WO2005089515A2

WO2005089515A2 - Methods for the treatment of synucleinopathies

Info

Publication number: WO2005089515A2
Application number: PCT/US2005/009396
Authority: WO
Inventors: Peter T. Lansbury; Zhihua Liu
Original assignee: The Brigham And Women's Hospital, Inc.
Priority date: 2004-03-18
Filing date: 2005-03-18
Publication date: 2005-09-29
Also published as: WO2005089515A3; US20050272722A1; WO2005089515A9

Abstract

Methods are provided of treating synucleinopathies, such as Parkinson’s Disease, Diffuse Lewy Body Disease and Multiple System Atrophy, comprising administering to a synucleinopathic subject a farnesyl transerase inhibitor compound.

Description

METHODS FOR THE TREATMENT OF SYNUCLEINOPATHIES

RELATED APPLICATIONS

Tliis application claims benefit under 35 U.S.C. 119(e) of the filing date of USSN 60/555,071 filed on March 18, 2004, the entire disclosure of which is incorporated herein by reference.

FEDERALLY SPONSORED RESEARCH This invention was made with Government support under NIH (National Institute of Health) Grant No. NS38375. The Government may have certain rights to this invention. FIELD OF THE INVENTION

The present invention relates to therapeutic approaches to the treatment of synucleinopathies, such as Par- inson's Disease (PD), Diffuse Lewy Body Disease (DLBD) and Multiple System Atrophy (MSA).

BACKGROUND OF THE INVENTION Synucleinopathies are a diverse group of neurodegenerative disorders that share a common pathologic lesion containing aggregates of insoluble α-synuclein protein in selectively vulnerable populations of neurons and glia. Certain evidence links the formation of abnormal filamentous aggregates to the onset and progression of clinical symptoms and the degeneration of affected brain regions in neurodegenerative disorders including Par?kinson' s disease, diffuse ?Lewy body disease and multiple system atrophy. The clinical treatments of these diseases include carbidopa-levodopa, anticholinergics and symptomatic medication, although for some synucleinopathies such as diffuse Lewy body disease a specific therapy does not exist. Most Par? inson's subjects that initially respond well to levodopa develop motor fluctuations and a "wearing-off ' phenomenon , within five years. Given the severe debilitating nature of these disorders and their prevalence there is a clear need in the art for novel approaches towards treating and managing these diseases.

SUMMARY OF THE INVENTION

The present invention relates to therapeutic approaches to the treatment of synucleinopathies, such as Parkinson's Disease (PD), Diffuse Lewy Body Disease (DLBD) and Multiple System Atrophy (MSA) by treatment with farnesyl transferase inhibitor compounds. h one aspect, the invention provides methods for treating a synucleinopathic subject by adα-iiriistering a composition comprising a farnesyl transferase inhibitor compound in a therapeutically effective amount. In some embodiments, the composition includes one or more farnesyl transferase inhibitor compounds disclosed herein, or one or more stereoisomeric forms or pharmaceutically acceptable acid or base addition salt forms thereof. In one embodiment, the composition includes one or more farnesyl transferase inhibitor compounds of Figure 5, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof.

In another aspect, the invention provides methods for treating a synucleinopathic subject by administering both a farnesyl transferase inhibitor compound and a second therapeutic compound in therapeutically effective amounts. The two compounds can be administered as a combination composition comprising both compounds. Alternatively, the two compounds can be administered separately (e.g. as two different compositions) either simultaneously or sequentially as described herein. In some embodiments,-the farnesyl transferase inhibitor composition includes one or more farnesyl transferase inhibitor compounds disclosed herein, or one or more stereoisomeric forms or pharmaceutically acceptable acid or base addition salt forms thereof. In one embodiment, the farnesyl transferase inhibitor composition includes one or more farnesyl transferase inhibitor compounds of Figure 5, or a stereoisomeric form or a pharmaceutically acceptable acid or base addition salt form thereof. In some embodiments, the second therapeutic compound includes, but is not limited to dopamine agonists such as Pramipexole, and Memantine, Aricept, and other acetycholinesterase inhibitors. According to the invention, FTI-277 lowers synuclein level in COS-7 cells and inhibits synuclein toxicity in SH-SY5Y cells. These cells are dopaminergic neuroblastoma cells and can be useful for analyzing Par-kinson's Disease pathogenesis.

It should be appreciated that aspects and embodiments of the invention described herein in connection with one farnesyl transferase inhibitor also may be practiced using two or more farnesyl transferase inhibitors (e.g., between 2 and 50, between 2 and 25, between 2 and 10, 2, 3, A, 5, 6, 7, 8, or 9). Similarly, aspects and embodiments of the invention described herein in connection with one other compound also may be practiced using two or more other compounds (e.g., between 2 and 50, between 2 and 25, between 2 and 10, 2, 3, 4, 5, 6, 7, 8, or 9). BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows that UCH-L1 membrane association is regulated by its fa nesylation. Figure 2 shows that C220S mutation abolished the inhibitory effect of UCH-L1 WT on α- synuclein degradation. Figure- 3 shows that farnesyl transferase inhibitor can rescue the α-synuclein toxicity in infected SH-SY5Y cells. Figure 4 shows that FTI-277 rescued α-synuclein toxicity in SH-S Y5Y cells by reducing the amount of α-synuclein accumulation. Figure 5 shows the formula of compound BMS 214662.

DETAILED DESCRIPTION

The invention provides methods, compositions and articles of manufacture for treating synucleinopathic subjects. Methods of the invention are useful to accelerate the degradation of α-synuclein, the accumulation of which is pathogenic in synucleinopathies. The invention provides methods for treating a synucleinopathic subject, including the step of administering to the synucleinopathic subject a therapeutically effective amount of a farnesyl transferase inhibitor compound or a therapeutical preparation, composition, or formulation of the compound such as^" those described herein, including those in the Claims, Figures, patents and publications listed herein. In preferred embodiments, the synucleinopathic subject is a human. one aspect of the invention is a method of treating a synucleinopathic subject is provided, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

II

in

IV or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein m,n,r,s and t are 0 or 1; p is 0, 1 or 2; N, and X are selected from the group consisting of oxygen, hydrogen, R¹, R² or R³; Z and Y are selected from the group consisting of CUR⁹, SO₂, S0₃, CO, C0₂, O, ΝR¹⁰, S0₂ ΝR¹¹,

CO R¹²,

or Z may be absent; R°, R', R^y, R^ιυ, R¹ \ R¹ , R^1J, R¹⁴, R^1D, R¹⁰, R¹ ', R¹⁸, R^ιy, R^ R ^I, R^z~, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl; R , R are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R , U is selected from the group consisting of sulfur, oxygen, ? R²⁴, CO, SO, S0₂, C0₂, NR²⁵ C0₂, NR²⁶ CONR²⁷, NR²⁸ S0₂, NR²⁹ S0₂ ?NR³⁰, S0₂ NR³¹, NR³² CO, CONR³³, P0₂ R³⁴ and PO₃ R³⁵ or U is absent; R¹, R², and R³ are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl (e.g. CO?NH₂) or substituted carbamyl further selected from CO?NH alkyl, CONH aryl, CO? H aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl; R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R¹, R², and R³ can be joined to form a cycloalkyl group;

R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)pQ wherein Q is NR³⁶ R³⁷, OR³⁸, or CN; and A, B, C and D are carbon, oxygen, sulfur or nitrogen with the provisos that:

1.^• When m is zero then V and W are not both oxygen or, 2. W and X together can be oxygen only if Z is either absent, O, ?NR , CHR ,

in formulas I and π, and V and X together can be oxygen only if Y is O, ?NR¹⁰, CHR⁹,

in formulas HI and IV or, 3. R ,23 may be hydrogen except when U is SO, S0₂, ?NR 25 , CO₂ oi

?NR ,28⁸ S0₂, or, 4. R⁸ may be hydrogen except when Z is S0₂, C0₂, or

In one embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein n is 1; r, s and t are 0 or 1; p is 0, 1 or 2; N, W and X are selected from the group consisting of oxygen, hydrogen, R¹, R² and R³ ;

Z and Y are selected from the group consisting of CHR⁹, S0₂, S0₃, CO, C0₂, O, -NR¹⁰, S0₂ NR¹¹, CONR¹², or Z may be absent; R⁶, R⁷, R⁹, R¹⁰, R^π, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²⁴, R²⁵, R²⁶, R²⁸, R²⁹, R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl; R⁴ and R⁵ are selected from the group consisting of hydrogen, halo, nitro, cyano and U- -R²³ ; U.is selected from the group consisting of sulfur, oxygen, ?NR²⁴, CO, SO, SO₂, C0₂,NR²⁵ C0₂, NR²⁶ CONR²⁷, ? R²⁸ S0₂, NR²⁹ S0₂ NR³⁰, S0₂ NR³¹, NR³² CO, CONR³³, PO₂ R³⁴ and PO₃ R³⁵ or U is absent; R¹, R² and R³ are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl and substituted carbamyl; R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R¹, R² and R³ may be joined to form a cycloalkyl group;

R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)pQ wherein Q is NR³⁶ R³⁷, OR³⁸ or CN; and A, B, C and D are carbon; with the provisos that V and W are not both oxygen; W and X together may be oxygen only if Z is either absent, O, ?NR¹⁰, CHR⁹, ~N(R¹ )~C(O)~, -N(R¹⁵)~S0₂ -; R²³ may be hydrogen except when U is SO, S0₂, NR²⁵ CO₂ or NR²⁸ S0₂ ; and R⁸ may be hydrogen except when Z is S0₂, C0₂, ~N(R¹⁵)~

SO₂, O_v NR²⁰ R²¹N NR²²

\// \// S or S .

In yet another embodiment of the invention the compound is selected from the group consisting of:

2,3,4,5-Tefrahydro-l-(lH-mddazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

8-CUoro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-4-(lH-imidazol-4-yl-methyl)-l-(l-l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)-2-methyl-4-(l-naphthalenylcarbonyl)-l-H-

1,4-benzodiazepine, hydrochloride;

2₅3,4,5-Tetrahydro-4-(l-naphthalenylcarbonyl)-l-[[l-(phenylmethyl)-lH-imidazol-5- yl]methyl]-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-(lH-irnidazol-4-yl-methyl)-4-(l-naphthalenylsulfonyl)-lH-l,4- benzodiazepine, hydrochloride;

(S)-2,3,4,5-Tefrahydro-l m-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H-l,4- benzodiazepine-4-carboxamide, hydrochloride; 2-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)-lH-l,4-benzodiazepin-4- yl]sulfonyl]benzoic acid, methyl ester, hydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenenylcarbonyl)-7-phenyl-lH- 1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-[3-(lH-imidazol-2-yl)proρyl]-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[3-Amino-3-(lH-imidazol-2-yl)ρroρyl]-2,3,4,5-tetrahydro-4-(l-naρhthalenylcarbonyl)-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-methyl-4-(l-napthalenylcarbonyl)-lH-

1,4-benzodiazepine, hydrochloride; (S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylmethyl)- 1H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH--Lmidazol-4-ylmethyl)-9-methyl-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-4-(lH-imidazol-4-ylmethyl)-9-methyl-l-(l-naρhthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihyrdochloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, trihydrochloride;

1 -[[2-Aminomethyl)- lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l - naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]acetamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-nitro-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH--hnidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-amino-lH-

1,4-benzodiazepine, dihydrochloride;

N-[2,3,4,5-Tefrahydro- -(lH-imidazol-4-ylmethyl)-4-(l.-naphthalenylcarbonyl>lH-l,4_- benzodiazepin-8-yl]benzamide, dihydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2₅3,4,5-Tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride; 7-Bromo-2,3,4_J5-tefrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naρhthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihydrochloride; l-[[l-(2-An-ιinoethyl)-lH-imidazol-5-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine-4- carboxylic acid, phenylmethyl ester;

2,3₅4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- lH-l,4-benzodiazepine; l,2,3,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H-l,4- benzodiazepine-4-carboxamide, dihydrochloride; 2,3,4,5,-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaleneylcarbonyl)-7-(l- piperidinylsulfonyl)- 1H- 1 ,4-benzodiazepine, monohydrochlori.de;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-pyridin-2-yl- lH-l,4-benzodiazepine, trihydrochloride; 7-(2-Furanyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, dihydroclύoride;

2,3,4,5-Tefrahydro-l-(lH-i-midazol-4-ylmemyl)-4-(l-naphmalenylcarbonyl)-7-(2-tMenyl)- lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahy(-ho-l-(lH-iιnidazol-4-ylmemyl)-4-(l-naphthalenylcarbonyl)-7-(4-pyridinyl)- lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-[3-(lH-imidazol-2-yl)propyl]-4-(l-naphthalenylcarbonyl)-7-phenyl- lH-l,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tetrahydro-4-(lH-imidazol-4-ylmethyl)-l-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihydrochloride; 8-Chloro-2,3,4,5-tetrahydro-4-(lH-imidazol-4-ylmethyl)-l -(-1 -naphthalenylcarbonyl)- 1H-

1,4-benzodiazepine, dihydrochloride;

2,3 ,4,5 -Tetrahydro-4-( 1 H-imidazol-4-ylmethyl)- 1 ,-( 1 -naρhthalenylcarbonyl-)-7-phenyl- 1H-

1,4-benzodiazepine, hy(.hocMoride; 2,3,4,5-Tetrahydro-l,4-bis(lH-imidazol-4-ylmethyl)-7- - phenyl-lH- 1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(m-imidazol-4-ylme l)-4-(l-naphthalenylmethyl)-7-phenyl-lH-l,4- benzodiazepine, trifluoroacetate;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme yl)-7-memoxy-4-(l-naphthalenylcarbonyl)-lH- l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine-7-carboxylic acid, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-5-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-cyclohexyl-

1H- 1,4-benzodiazepine, 2.5 hydrochloride;

7-Butyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride; l-[[2-(Aminomethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-[N,N- bis(phenyl-methyl)amino]-lH-l,4-benzodiazepine, trihydrochloride; N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]phenylsulfonamide, dihydrochloride;

N-Phenyl-2₃3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-

1 ,4-benzo-diazepine-7-carboxamide, dihydrochloride; N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-methylbenzamide, dihydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-4-methylberιzamide, dihydrochloride;

3-Chloro-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzo-diazepin-8-yl]benzamide, dihydrochloride;

7-Bromo-2,3 ,4,5,-tetrahydro- 1 - [ [2-[(dimethylamino)-methyl] - lH-imidazol-4-yl]methyl] -4-

(l-naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-(4-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1H- 1 ,4-benzodiazepine, dihydrochloride; 7-(3-Aminophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- - =• - - naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

^"l-Methyl-Nr[2,3,4,5-tefrahydro-lr(lH-irm^^"azol-4-ylmemyl)r4-(l-naphmalenylcarbonyJ)_^ lH-l,4-benzodiazepin-8-yl]-lH-ρyrrole-2-carboxamide, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-furancarboxamide, dihydrochloride;

7-(3-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l ,4-benzodiazepine, dihydrochloride;

2-Methyl-N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepin-8-yl]benzamide, dihydrochloride; N-Phenyl-N'-[2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)-

1H-1 ,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)-7-(3-pyridinyl)-

1H- 1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-9-methoxy-4-(l-naphthalenylcarbonyl)-lH- 1,4-diazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-3-(2-hydroxyethyl)-l-(lH-imidazol-4-yhnethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, trifluoroacetate;

2,3,4,5-Tefrahydro-4-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate; (S)-2,3,4,5-Tefrahydro-l-(lH-i-midazol-4-ylme l)-4-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-4-(lH-imidazol-4-ylmethyl)-l-(l-naphthalenylcarbonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, 1.5 hydrochloride;

7-Bromo-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxamide, trifluoroacetate;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, hydrochloride; 4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-7-ρhenyl-3-( heny?ljmethyl)-lH-

1 ,4-benzodiazepine., trifluoroacetate; 4-Acetyl-7-bromo-3-[(4-6hlorophenyl)methyl]-2,3,.4,5-tetrahydro- 1 -(lH-imidazol-4- ylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

N-Cyclohexyl-N'-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1H- 1 ,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,2-Dimethyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepin-8-yl]propanamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylsulfonyl)-7-phenyl-lH-

1 ,4-benzodiazepine, monohydrochloride; 4-Acetyl-7-bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(2- naρhthalenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(l- naphthalenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; ' 7-(2-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, monohydrochloride; l-Methyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, trihydrochloride; N-[2,3,4,5-tefrahydro-l-(lH-midazol-4-y-knethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-4-morpholinecarboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-methylbutanamide, dihydrochloride; ^■ l,2,3,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-N,N,7-triρhenyl-4H-l,4-2 5 benzodiazepine-4-carboxamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y--me l)-7-ρhenyl-4-[(4-phenyl-l,2,3-1hiadiazol-5- yl)carbonyl]-lH-l ,4-benzodiazepine, trifluoroacetate;

8-[[(Cyclohexylam o)carbonyl]amino]-2,3,4,5-tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)- 1H- 1 ,4-benzodiazepine-4-carboxylic acid, 1 , 1 -dimethylethyl ester;

2,3,4,5-Tefrahydro-l-(lH-inύdazol-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3-

(phenylmethyl)-lH-l,4-benzodiazeρine-4-carboxylic acid, 1,1-dimethylethylester;

7-Bromo-l,2,3,4-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-5H-l,4- benzodiazepin-5-one, dihydrochloride; 2,3,4,5-Tetf ahydror 1 -( lH-imidazol-4-ylmethyl)-4- [ 1 -oxo-3-( 1 -piperidinyl)propyl] -7-phenyl-

1H-1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5_^Tefrahydro-i iH-imidazol-4-ylmemyl)-7-phenyl-4-(4-qmnolinylcarbonyl:)-lH-l,4- benzodiazepine, trihydroc-hloride;

4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, trihydrochloride; . . ..

(S)-4- [2-(Dimethylamino)- 1 -oxo-3 -phenylpropyl] -2,3,4,5 -tetrahydro- 1 -(lH-imidazol-4- ylmethyl)-7-phenyl-lH-l ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-4-[4-hydroxy-3-(4-morpholinyl-methyl)benzoyl]-l-(lH-imidazol-4- ylmethyl)-7-phenyl- 1H- 1 ,4-benzodiazepine, trihydrochloride; (S)-2,3,4,5-Tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-2-pyrrolidinyl)carbonyl]-

7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[[2-(proρylthio)-3- pyridinyl] carbonyl] - 1H- 1 ,4-benzodiazepine, trihydrochloride;

4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH-l,4-benzodiazeρine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(ρhenylthio)-3- pyridinyl]carbonyl]-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3- pyridinyl]carbonyl]-7-ρhenyl-lH-l,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(5-ρhenyl-4- oxazolyl)carbonyl]-lH-l ,4-benzodiazepine, dihydrochloride; 4-Acetyl-2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-3- furanyl)carbonyl]-lH-l ,4-benzodiazepine, dihydroc-hloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl-lH- 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-y--memyl)-4-[4-(4-morpholmylmethyl)benzoyl]-7- phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-i.ι-mdazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl- lH-l,4-benzodiazepine, dihydrochloride; - .2,3,4,5-Tefrahydro-l-(lH- ιidazol-4-ylmethyl)-4-[l-oxo-3-(phenylsulfonyl)propyl]-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride; - : 2,3,4,5-Tefrahydro--l-(lH-imidazol-4_rylm,ethyl)-7-phenyl-4-(3~ρyridinylacetyl) H-l,4-- benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahy<-ho-l-(lH-imidazol-4-ylmemyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)-lH- l,4-benzodiazepine, etrahydrochloride;

2, 3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl-H-

1,4-benzodiazepine, trihydrochloride;

4-[(2-Chloro-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-ρyridinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

4-[(2,6-Dimemoxy-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1H-1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(2-pyrazinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

4-(2-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[3-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(l- ρhenylcyclopropyl)carbonyl]-lH-l,4-benzodiazepine, dihydrochloride;

4-[(Bicyclo[4.2.0]octa-l,3,5-trien-7-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-in-iidazol-4- ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepine, dihydrochloride; 4-Benzoyl-2,3,4,5-tefrahycho-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-(2-Cmorobenzoyl)-2,3,4,5-tefrahyά^o-l-(m-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,3-Dichlorobenzoyl)-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4- benzodiazepine, dihydrochloride;

N-[2-[[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]phenyl]-acetamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-TettShydro-l-(lH-imidazol-4-ylmethyl)^'-4-(2-methoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; . .-

4-(2,3-Dimethoxybenzoyl)-2,3,4_i5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l₅4- benzodiazepine, dihydrochloride;

4-(2,4-Dimethoxybenzoyl)-2,3 ,4,5 -tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4- benzodiazepine, dihydroc-hloride;

4-(2,5-Dimemoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,6-Dimethoxybenzoyl)-2,3 ,4,5-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-phenyl- 1 H- 1 ,4- benzodiazepine, dihydrochloride; 4-(2,3-Dihy(koxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-([l,r-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-

1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-phenyl-l H-l ,4- benzodiazepine, dihydrochloride;

4-(2,3-Dimethylbenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(3-C orober^oyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3,4-D emoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-in-ιidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydroc-hloride;

4-(3,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(l,2-Dioxo-2-ρhenylethyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydroc-hloride; 4-[(2-Ethoxy-l-naphthalenyr)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-" - phenyl-lH-l,4-benzodiazepine, ^"dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbόnyl)-7-phenyl-lH--

1 ,4-benzodiazepine, dihydrochloride;

4-(Fluoroρhenylacetyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(Diphenylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2₅3,4,5-Tetrahydro-4-(2-hydroxy-l-oxo-2-phenylpropyl)-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-2-ylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-3-ylcarbonyl)-7-phenyl-lH-

1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-5-ylcarbonyl)-7-ρhenyl-lH- 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-lH-indol-2-yl)carbonyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

4-(2-Benzo--uranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- 1 H- 1 ,4- benzodiazepine, N-oxide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH--unidazol-4-ylme yl)-7-phenyl-4-(2-ρyridinylcarbonyl)-lH-l,4- benzodiazepine, trihydroc-hloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-( 1 -isoquinolinylcarbonyl)- 1 H-

1,4-benzodiazepine, trihydrochloride;

4-(3-CUoro-2-nifrobenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH- 1,4-benzodiazepine, dihydroc-hloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-nitrobenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-in-ύdazol-4-ylmethyl)-4-(3-memoxy-2-mtrobenzoyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(^:lH-iιnidazol-4-ylmemyl)-4-(lH-indor-4-ylcarbonyl)-7-phenyl-lH-

1 ,4-benzodiazepine,- dihydrochloride;

4-[(2,6-Dihydroxy-3-ήaphthalenyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- -- . - - ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-(lH-Benzimidazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine,- trihydrochloride;

4-(lH-Benzotriazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7- phenyl- 1H-1 ,4-benzodiazepine, trihydrochloride; N-[3-[[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazeρin-4- yl]carbonyl]phenyl]-acetamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxo-2-phenylpropyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-[2-(Dimethylamino)benzoyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepine, trihydrochloride;

4-(3-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-(2-hydroxy[l,l '-biphenyl]-3-ylcarbonyl)-l-(lH-imidazol-4-ylmethyl)-

7-phenyl-lH- 1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahy⁽ho-l-(lH-i-n-udazol-4-ylmethyl)-4-[(2-me oxy-l-naphthalenyl)carbonyl]-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-4-[(2-hyά :oxy-4-quinolinyl)-carbonyl]-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2-[[2,3,4,5-Tefrahydro-l-(lH-irm^azol-4-ylmemyl)-7-ρhenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]benzamide, dihydrochloride;

N-(l,l-Dimethylethyl)-2-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl]carbonyl]benzamide, dihydroc-hloride;

N-(4-Fluorophenyl)-N'-[3-[[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1 ,4-benzodiazepin-4-yl]carbonyl]phenyl]urea, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-iιnidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H- benzopyran-8-yl)carbonyl]-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]-

IH- 1,4-benzodiazepine, dihydrochloride;

4-(2-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[[(4- methylphenyl)sulfonyl] amino]benzoyl]-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinohnylcarbonyl)- 1 H- 1 ,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 4-(Benzo[b]thiophen-2-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydrochloride;

4-[[4-(Dimethylamino)-l-naρhthalenyl]carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl- IH- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(lH-purin-6-ylcarbonyl)-lH- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(5-methyl-l-ρhenyl-lH-ρyrazol-4- yl)carbonyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH---midazol-4-ylmethyl)-4-[2-(2-methylphenyl)-l-oxopropyl]-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(tetrahydro-4-phenyl-2H- pyran-4-yl)carbonyl]-lH-l ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme yl)-4-[2-(mem^ phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3 ,4, 5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1 ,4- benzodiazepine, N-oxide, dihydrochloride;

N-Methyl-N-(2-pyridinylmethyl)-2-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepin-4-yl]carbonyl]benzamide, trihydrochloride;

2,3,4,5-Tefrahy(-ho-l-(lH-imidazol-4-ylmethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1:2); 4-[3-(3,4-Dimethoxyphenyl)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-

1H- 1,4-benzodiazepine, trifluoroacetate (1:2);

4-([l,l^,-Biphenyl]-4-ylacetyl 2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

4-([l,l'-Biρhenyl]-2-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-phenyl4-quinolinyl)carbonyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :3); 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :3);

4-(9H-Fluoren-9-ylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

(S)-4-[2-(Dimethylamino)-l-oxo-3-phenylpropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:3);

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-oxo-4-phenyl-3- oxazolidinyl)acetyl]-lH-l,4-benzodiazepine, trifluoroacetate (1:2); 4-(9-Acridinylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:3); 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(3-phenoxybenzoyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-[[4'-(trifluoromethyl)[l,l ^,-biphenyl]-2- yl]carbonyl]-lH-l,4-benzodiazepine, trifluoroacetate (1:2); 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(4-phenoxybenzoyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxo-4-phenylbutyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]- lH-l,4-benzodiazepine, trifluoroacetate (1:2); 2,3,4,5-Tefrahydro-l-(lHⁱimidazol-4-ylmethyl)-4-[2-[(phenylmethyl)amino]benzoyl]-lH-

1,4-benzodiazepine, frifluoroacetate (1:3); l,2,3,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-N,N-diphenyl-4H-l;4-benzodiazepine-4- carboxamide, hydrochloride; l,2,3,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)-a,7-diphenyl-4H-l,4-benzodiazepine-4- acetic acid, methyl ester, hydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-i-n-ύdazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; (R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-

1H-1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride;

(^)-4-Acetyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(phenylmethyl)-

1 H- 1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-4-[ [2-(dimethylamino)ethyl] sulfonyl] -2,3 ,4,5 -tetrahydro- 1 -( 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetτahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(l,2,3,4-tetrahydro-l- quinolinyl)carbonyl] - 1 H- 1 ,4-benzodiazepine, monohydrochloride;

N-Ethyl-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,7-diphenyl-4H-l,4- benzodiazepine-4-carboxamide, monohydrochloride; 4-[(2,3-D ydro-lH-indol-l-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tefrahydro-l-(lH-irmdazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride; (R)-4-[[2-(Dimethylammo)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1);

[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(l-methyl-lH-imidazol-5-yl)methyl)-4-(methylsulfonyl)- 3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-

3-(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

4-[2-(4-Cmorophenyl)-l,2-dioxoethyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, hydrochloride; 4-(l,2-Dioxoproρyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-pheflyl-lH-l,4- benzodiazepine, hydrochloride; "^■ 2,3,4,5-Tefrahydro-l-(lH-ήhidazol-4-ylmethyl)-4-[2-(4-nitroρhenyl)-l,2-dioxoethyl]-7- - - phenyl- 1 H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(4-methoxyphenyl)-l,2-dioxoethyl]-7- ^• ρhenyl-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3,3,3-trifluoro-l,2- dioxopropyl)-lH- 1,4-benzodiazepine, trifluoroacetate (1:2); R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylacetyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(2-lH-imidazol-4-ylethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzbdiazepi-ne, monohydrochloride;

8-[(Cyclohexylcarbonyl)amino]-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-4H-l,4-benzodiazepine-4-carboxylic acid, methyl ester, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl-l-piperidinecarboxamide, dihydrochloride;

(U)-7-Cyano-l,2,3,5-tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazeρine-4-carboxylic acid, ethyl ester, hydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)- lH-l,4-benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride; (^)-7-Cyano-4-[[2-(dimethylamino)emyl]sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- morpholinyl)ethyl] sulfonyl] -3 -(phenyhnethyl)-4H- 1 ,4-benzodiazepine, dihydrochloride; N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride,

8-[(Cyclohexylcarbonyl)amino]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N-phenyl- lH-l,4-benzodiazepine-4-carboxamide, dihydroc-hloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methylρhenyl)sulfonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-ύιιidazol-4-ylme l)-3-(phenylmethyl)-^^ benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride; (3R)-7-Bromo-l-[cyano(lH-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro^:-^:4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(3R)-l-[2 Amino-l-(lH--imidazol-4-yl)e l]-2,3,4,5-tefra£ydro-4-(methylsulfo^

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-(Dimethylamino)-l-(lH-imidazol-4-yl)ethyl]-2,3^4,5-tetrahydro-4- (methylsulfonyl)-3-(phenylmethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-Amino-l-(lH-imidazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-(pimethylamino)-l-(lH-in-udazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazeρine, dihydrochloride; 7-Cyano- 1,3,4,5 -tetrahydro- 1 -( 1 -methyl- 1 H-imidazol-5-ylmethyl)-3 -(phenylmethyl)-4-

(phenylsulfonyl)-2H- 1 ,4-benzodiazepin-2-one, monohydrochloride;

7-Cyano-l,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-2H- 1 ,4-benzodiazepin-2-one, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- phenylethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-3-(cyclohexylmethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 7-Bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(S)-7-Bromo-3-(cyclohexylmethyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; 7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-methoxyphenyl)methyl]-4-

(methylsulfonyl)-lH-l,4-benzodiazeρine, dihydrochloride;

4-Acetyl-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-hydroxyphenyl)methyl]-4-

(methylsulfonyl)-lH- 1,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(3- pyridinylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-8-(hydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

2-,3,45-Tefrahy ro-l-(lH-imidazol-4-y?hiiethyl)-4-(l-naphthalenylcarbonyl)ⁱ8- ^'"-

(phenoxymethyl)-lH-l,4-benzodiazepine, dihydrochloride;

N-Cyclohexyl-2,3,4,5-tetrahydro-l-(l-H-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine-8-carboxamide, dihydrochloride;

N-(Cyclohexylmethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine-8-carboxamide, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)-N -

(phenylmethyl)-lH-l,4-benzodiazepine-8-carboxamide, dihydrochloride; (R)-4-Acetyl-7-[2-[(dimethylammo)methyl]phenyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(R)-4-Acetyl-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-

1,4-benzodiazepine, monohydroc-hloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxobutyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxopropyl)-3-

(phenyl ethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- pyridinylacetyl)-lH-l,4-benzodiazepine, dihydrochloride; (U)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-4-[(l-methylethyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; 5 0R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

[(trifluoromethyl)sulfonyl] - IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- 10 (phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tefrahyd o-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(phenylmethyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride; 15 ^"(R)-7-Cyano-4-[(4-fluoroρhenyl)sulfonyl]-2,3,4,5-tetralιydro-l-(lH-imidazol-4-ylmethyl)-'3~

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; - ^■■ - - .. - ?R)-7-Cy ιo-4-[(3-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazdl-4-ylmethyi)-3--

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydr©-l- lH-imidazol-4-ylmethyl)-4-[(l-memyl-lH-imidazol-2- 20 yl)sulfonyl] -3 -(phenylmethyl)- IH- 1,4-benzodiazepine, dihydrochloride;

0R)-4-[(3-Bromophenyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-N-[5-[[7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH- l,4-benzodiazeρin-4-yl]sulfonyl]-4-methyl-2-thiazolyl]acetamide, dihydrochloride; 25 4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3- henylmethyl)-7-(4-pyridinyl)-

1H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-ρhenyl-l,2-dioxoethyl)-7-(4- pyridinyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2- 30 (trifluoromethoxy)benzolyl] - 1 H- 1 ,4-benzodiazepine, trihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7- phenyl-3-(phenylmethyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylacetyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; 4-(2-BenzotHazolyl)-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)-7-(3-pyridinyl)-4-

(trifluoroacetyl)-lH-l,4-benzodiazepine, trihydrochloride; 5 2,3,4,5-Tefrahydro-l-(lH-irnidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3- pyridinyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

7-Bromo-3-[(l,l-dimethylemoxy)methyl]-l,2,3,4-tefrahydro-l-(lH---midazol-4-ylmethyl)-

5H-l,4-benzodiazepin-5-one;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-0 (phenoxymethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tetrahydro-3-(hydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-3-[(l,l-dimethylethoxy)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H-l ,4-benzodiazepine; 5 [7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4---- : •= benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester, trihydrochloride; - = t4-Acetyl-7-bromort2,3,4,5-tefrahydro -(lH ιmidazol-4-ylmemyl)-3 henylmethyl) H--τ l,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester;

N-[4-Acetyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)-lH-l,4-0 benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-y-h-nethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)- lH-l,4-benzodiazepine-7-carbonitrile, monohydrochloride; 5 7-Bromo-l ,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l ,4- benzodiazepine-4-acetamide;

7-Bromo-4-[(dimethylamino)acetyl3-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Bromo-4-(l,2-dioxopropyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-0 (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-(cyclopropylcarboonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H-l ,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3,4,5-tefrahydro-l,4-bis(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepine, dihydroc-hloride;

7-Bromo-l,2,3,5-tefrahydro-l-(lH-imidazol-4-y-bue yl)-N,N-(-limethyl-3-(phenylmethyl)-

4H- 1 ,4-benzodiazepine-4-sulfonamide, monohydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydrό-l-(lH-imidazol-4-yhnethyl)-N,N-dimethyl-3-

(phenylmethyl)-4H- 1 ,4-benzodiazepine-4-carboxamide, monohydrochloride;

N,N-Diemyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l ,4-benzodiazepine-7-carboxamide, monohydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(l -phenyl- lH-tetrazol-5-yl)-lH-

1,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- pyrazinylcarbonyl)-4H-l ,4-benzodiazepine, monohydrochloride; (R)-4-[7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- - benzodiazepinⁱ4-»yl]-4-oxobutanoic acid, methyl ester, monohydrochloride;-,,

(R)-7-Gyanor2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-moφholinylcarbonyl)-3--

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(^)-7-Cyano-2,3,4,5.-tefrahydro-l-(lH-iιnidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-(l- pyrrolidinyl)ethyl]sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethy^-lH-l^-benzodiazepine, dihydrochloride; ,

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(3-pyridinylmethyl)-4-(2- tMenylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(propylsulfonyl)-3-(3- pyridinylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- pyridinylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(2- pyrimidinyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

[(trifluoromethyl)sulfonyl]-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(ρhenylmethyl)-4-

(trifluoroacetyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; (R)-2,3,4,5-Tetrahyα^o-l-(lH-in-ύdazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7- (4-pyridinyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylme yl)-3-(phenylmethyl)-7-(4-pyridmyl)-4-(2- thienylsulfonyl)- 1 H-l ,4-benzodiazepine, dihydroc-hloride; (R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(ρhenylmethyl)-4-(phenylsulfonyl)-7-

(4-pyridinyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tefrahy(-ho-l-(lH-imidazol-4-ylmemyl)-3-(ρhenylmethyl)-4-(ρroρylsulfonyl)-7- (4-pyridinyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(3,5- dimethyl-isoxazol-4-yl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-4-[(4-cyanoρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)- IH- 1,4-benzodiazepine, dihydrochloride;

(R)-7-Cytoo-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2,2,2- trifluoroethyl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydroτl--(lH-imidazol-4-ylmethyl)-4-[(4- - .-■£ - - methoxyphenyl)sulfonyl] -3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

N-[[7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-lH-l,4- benzodiazepin-3-yl]methyl]benzamide, dihydrochloride; .

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-

(phenylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-N,N-dimethyl-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-

(phenylmethyl)-4H-l,4-benzodiazepine-4-sulfonamide, hydrochloride; (R)-7-Chloro-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-

3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tefrahy(-ho-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(phenylsulfonyl)- 3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, tetrahydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidaz yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trihydrochloride;

(R)-7-Cωoro-2,3,4,5-tefrahydro-l-(l-me yl-imidazol-5-ylmethyl)-4-[(2-mo-φhohn-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-CUoro-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-morpholin-4-yl- ethyl)sulfonyl] -3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-CUoro-4-[(dimemylamino)sulfonyl]-l-[(l-me&yl-lH-imidazol-5-yl)methyl]-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-C-hloro-2,3,4,5-tefrahydro-l-(l-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piρeridin- 4-yl-ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(^)-7-Bromo-2,3,4,5-tefrahycko-l-(l-memyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin-

4-yl-ethyl)sulfonyl]-3-(ρhenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(^)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxylic acid, isopropyl ester, hydrochloride; (R)-7-Bromo 2,3,4,5-tefraKydro-4-[[2-(lH-im^^ ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; - - .(R)-7-Cyano-2,3-,4_r5-tefrahydro-l-(lH-imidazol-4-ylmeth}4)-4-(proρylsvtlfonyl)--?-(3-;- - - pyridinylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

7-Bromo_^2,3,4,5-tetrahydro-l-(lH-in--ddazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazeρin-5-one, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-l-ylacetyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH- 1,4-benzodiazepine, trifluoroacetate; l,2,4,5-Tefrahycho-'l-(lH-imidazol-4-ylmemyl)-2-(2-phenylemyl)-3H-l,4-benzodiazepin-3- one; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-(2-ρhenylethyl)-lH-

1,4-benzodiazeρine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(4- pyridinylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(ρhenylmethyl)- lH-l,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-rmidazol-4-ylmethyl)-N,N-dimethyl-3-(3- ρyridinylmethyl)-4H- 1 ,4-benzodiazepine-4-carboxamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, dihydrochloride; (R)-2,3,4,5-Tetrahydro- 1 -(1 -(4-cyanophenylmethyl)-imidazol-5-ylmethyl)-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine-7-carbomtrile, hydrochloride;

(R)-2,3,4,5-Tetrahydro- 1 -(1 -(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine-7-carbomtrile, hydrochloride; 5 (R)-4-Benzoyl-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)- lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-me l-lH-imidazol-5-yl)methyl]-3-(pyridin-3- ylmethyl)-4-(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(TR)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-inιidazol-5-yl)memyl]-3-(pyridin-3- 10 ylmethyl)-4-(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-yl)me yl]-3-(pyridin-3-ylmethyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro- -(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-

(phenyhnethyl)-lH-l,4-benzodiazepine; 15 .- l,2,3,5--Tefrahydro-r-(lH-imidazol-4-ylmethyl)-N-(l-naphthalenyl)-7-phenyl-4H-l,4-

" benzodiazepine-4-carboxamide, monohydrochloride; ^{' ~}

^'- - (S)-7-Bromo-2,3A5 eirahydro-l-(ffi^{^}^ - - :- -

- (phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

'•. N-[-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme l)-4r(2,3-dimethylbenzoyl)-lH-l,4- - 20 benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-N-[2-(dime ylan iιιo)ethyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N- methyl-3-(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxamide, trifluoroacetate (1 :2);

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; 25 (R)-7-Cyano-4-(2-fiιranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- IH- 1,4-benzodiazepine, trifluoroacetate (1:1);

(R)-7-Cymo-2,3,4,5-tefrahydro-l-(lH--buidazol-4-ylmemyl)-4-[(4-mfrophenyl)sulfonyl]-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, trifluroracetate;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[4-(4-methyl-l- 30 piperazinyl)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l ,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[(4- dimethylamino)phenyl] sulfonyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l ,4-benzodiazepine, dihydrochloride; (^)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(3- pyridinylsulfonyl)-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH-

1,4-benzo-diazepine, dihydrochloride; 5 (R)-7-Bromo-2,3,4,5-tefrahydro-l-[(l-methyl-lH-in idazol-4-yl)methyl]-4-(methylsulfonyl)-

3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(^)-4-[[3-(Dimemylamino)propyl]sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-

7-phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- 10 benzodiazepine, trihydrochloride;

4-Butyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride;

(R)-7-Bromθτ2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφhoKnyl)ethyl]sulfonyl]-3-(pheny-hue yl)-lH-l,4-benzodiazepme, dihydrochloride; 15. (R)-7-Bromo-2A4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-[[2-(4-^' moφholinyl)emyl]sulfonyl]-3-(pheny?-memyl)-lH-l,4-benzodiazepine, dihydrochloride; -

(R)-7-Cyano-l-^"(lH--h-mdazol-4-ylmelhyl)-4-(4-moφholinylsulfony

1,4-benzodiazepine, monohydrochloride; ■• - (R)-7-Cyano-l-[(l-memyl-lH-imidazol-5-yl)methyl]-4-[(4-moφhoUnyl)sulfonyl]-3- 20 (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-ammophenyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol^-ylmethyl)-4-[(4-ρyridylthio)acetyl]-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; 25 N-(4-Chlorophenyl)-N'-cyano- 1 ,2,3,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl-4H-

1 ,4-benzodiazepine-4-imidamide, monohydrochloride;

4-Acetyl-7-bromo-l,2,4,5, 1 ',3'-hexahydro-l-(lH-imidazol-4-ylmethyl)spiro[3H-l,4- benzodiazepine-3,2'-[2H]indene], dihydrochloride;

7-Bromo-4-[3-(dime ylamino)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- 30 ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1 : 1);

(R)-2,3,4,5-Tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-(ρhenylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride;

2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-ρhenyl-

3-(pyridin-3-yl-methyl)-lH-l,4-benzodiazepme, hydrochloride (1:1.5), trifluoroacetate 35 (1:0.75) salt; 4-[4-(Fluoroρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-2-(2- ρhenylethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)-lH-l,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-[[2-(l- moφholinyl)ethyl] sulfonyl] -3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahycho-l-(lH-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(4- bromophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahy(ko-l-(lH--unidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(thiazol- 4-ylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-y?lmethyl)-4-(propyl-sulfonyl)-3-(thiazol-

4-ylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH--mιidazol-4-ylmethyl)-4-(propylsulfonyl)-3-(4- bromophenylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride; (R)-7-BfΘino-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)r.4-

(methylsulfonyl)-lH- 1,4-benzodiazepine, trihydrochloride; ^• - ■- ^'

-- ^)-7-Brόrho-2,3,4,5-tefrahydfαΛ-(lH^ ylmethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazeρine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(ρhenyl-sulfonyl)-3-(4-- . cyanophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(TR)-7-Cyano-4-[(N-methyl-N-phenylmethyl)aιmnosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-

3 -(phenylmethyl)- 1 H-l ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-4-[N-(tetrahydroisoquinolinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(2- thienylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride; cis-2,3,4,5-Tefrahydro-l,5-bis(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)-lH-l,5- benzodiazepine-2-carboxylic acid ethyl ester, trifluoroacetate (1:2);

(R)-7-Cyano-4-[(N-ρiρeridinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-(phenylmethyl)- lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-l-methyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-

(2-thienylsulfonyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-[[2-

(dimethylamino)ethyl]sulfonyl]-lH-l,4-benzodiazepine, trihydrochloride; (R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-l-memyl-iιnidazol-5-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, hydrochloride;

N-(Cyano)-N'-methyl-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4H-l,4- benzodiazepine-4-imidamide, hydrochloride; (R)-7-Cyano-4-[(2- frophenyl)-sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyl-methyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

R)-7-Cyano-4-[(4-memyl-phenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-

3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-(butylsulfonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-trifluoro-methylphenyl)sulfonyl] -2,3 ,4,5 -tetrahydro- 1 -( lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

( )-7-Cyano-4-[(2-trifluoromethoxyphenyl)sulfonyl]-2,3,4,5-tetrahydro-l -(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazeρine, hydrochloride; -(R)-7-Cyano-4-[(2-memoxy-carbonylphen^)sulfonyl]-2,3,4,5-tefrahy(kori-(lH-imidazol-4-

- ylme yl)-3- heny?huethyl)-lH-l,4-beήz5diazepiner?hydrochloride; :^:(R)-^"7-Cyano-4-[(2-memyl-sulfonylphen^ ylmethyl)-3-(phenylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l.,(lH-imidazol-4-ylmethyl)-3-(phenylmethy-l)-4-(((4- methylsulfonyl)-phenyl)ι-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4- trifluoromethyl)-phenyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3- methoxypropyl)-sulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3,4- dimethoxyphenyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((4-fluorophenyl)methyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-[(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]-l-[(lH-imidazol-4- yl)methyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine; l,2,3,4-Tetrahydro-7-bromo-4-[(lH-imidazol-4-yl)methyl]-2-phenylmethyl-l-

(methylsulfonyl)quinoxaline; (R)-7-Cyano-2,3,4,5-tefrahyc o-l-(lH-imida

4-yl)methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine; 5 (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahyαro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3- methylthioproρyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(((3- 0 methylthioxo)-propyl)-sulfonyl)-lH-l ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahyαjo-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylsulfonyl)-ρropyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- methylpropyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine; 5 ^{' T}--~ (R)-7-Cyano-2,3,4,5-tetrahyάxo^" -(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-=-4-3O

(cyclopentylsulfonyl)-lH-l,4-benzbdiazepine; .

- .^{"■ "} (R)-7-Cyano-2,34₎5-tefrahydro-l (lH4midazol-4-ylmethyl)-3-(ρhenylmethyl)-4^ -; trifluorobutyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

( )-7-Cyano-2,3,4,5-tefrahy(ho-l-(lH-inιidazolr4-ylme l)-3-(phenylmethyl)-4-0 ((phenylmethyl)÷sulfonyl)-lHrl,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-[[2-(5-(N- benzoyl)-aminomethyl)-thienyl]-sulfonyl]-lH-l,4-benzodiazepine . (R)-7-eyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-[[2-(l-(3- chloro-5-methyl-ρyridin-2-yl))-pyrrolyl] -sulfonyl] - 1 H- 1 ,4-benzodiazepine; 5 (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[((3- methyl-l,2,4-oxadiazol-5-yl)-phenyl)-sulfonyl]-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2,5-0 dimethoxyphenyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-[(N-tefrahydroquinolinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N,N-bis-[l -(2-methylpropyl)amino]-sulfonyl]-l-[(lH-imidazol-4- yl)methyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-4-[(N-memyl-N-phenyl)aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylme yl)-3-(2-(2,6-dimethylρhenyl)- ethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahy(ko-l-(l-(N-ρhthalimidoethyl)-imidazol-5-ylmethyl)-3-

(phenylmethyl)-4-(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahycho-l-[(2-(N ,N-dimethylammo)-ethyl)-imidazol-5-ylmethyl]-3-

(phenylmethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-aminoemyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)- 4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(TR)-4-(methanesulfonyl)-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-y?hne1hyl)-3-(phenylmethyl)- lH-8-oxo-pyrimidino[4,5-e]-l,4-diazepine;

(R)-7-Cyano-2,3,4,5-tefrahy(-ho-l-(lH-i-tmdazol-4-ylmethyl)-3-((4-(2-methoxyethoxy)- ρhenyl)methyl)-4-(phenylsulfonyl)-lH-l,4-benzodiazepine; ( )-7-Cyano-2,3A5-tefrahydro-?t-(lH-imid^ ethoxy)-ρhenyl)methyl)-4-(phenylsulfonyl)-lH-l,4-benzodiazepine;

( )-7-Cyaho-2,3,45 efrahydrό^l^lH-imM r ^"

(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5τtefrahydro-l-(lH-imidazol-4-ylsulfonyJ)-3^(phenylmethyl)-4- (propylsulfonyl)-lH-l,4-benzόdiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2-. thienylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)- -phenyl-ethyl]-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4- (phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-ρhenyl-ethyl]-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-ρhenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4- (propylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)- i -phenyl-ethyl]-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tarahydro-l-(lH-imidazol-4-ylmethyl)-a--(S)-[(S)-l-ρhenyl-ethyl 4-

(methylsulfonyl)- 1 H^ 1 ,4-benzodiazepine; ■- 7-Cyano-2,3,4₅5--tefrahyd#o-l-(lH-u^^

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-.yhnethyl)-3-(S [(S)-l-ρhenyl-ethyl]-4- .- (phenylsulfonyl)τlH- 1,4-benzodiazepine; . - - ■.. ^•• . -.-.

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-((2- tbienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-y--methyl)-3-(R)-[(R)-phenylcyclopropyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcycloproρyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;.

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcycloproρyl)-4-

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)-lH-l ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(propylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahyάro-l-(lH-i-tmdazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4-

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4-

((2-thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-ρhenylcycloρroρyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-

(ρropylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-ρhenylcycloρropyl)-4- (phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-

((2-thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-ρhenylcycloproρyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3 4,5-tetr-ahydro-l -(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-phehylcycloproρyl)-4-

(propylsulfonyr)-lH-l,4-benzodiazepine; ^■ •

^"• . 7-Cyano-2,3,4,-5-tefrahydro ^1H-im

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmβthyl)-3-(S)-[(S)-ρhenylcyclopropyl)-4- - ((2-thienyl)-sulfonyl)-lH- 1,4-benzodiazepine; ^■: . ..

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5-

(pyridin-2-yl))-thienyl)-sulfonyl])-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3r(phenylmethyl)-4-[(2-(5-(l,2- isoxazol-3 -yl))-thienyl)-sulfonyl])- IH- 1 ,4-benzodiazepine; (R)-7.Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4- (propylsulfbnyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydxo-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH- 1 ,4-benzodiazepine; R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4- (methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahy(ho-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4- (propylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4- ((2-thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -(ρhenylmethyl)-4-((l - oxoethyl)-amino)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4- (methanesulfonylamino)-lH-l,4-benzodiazepine;

( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (phenylsulfonylamino)-lH-l,4-benzodiazepine. In another embodiment of the invention the compound has the formula:

wherein Ri is selected from Cl, Br, phenyl, pyridyl or cyano and R₂ is selected from substituted aralkyl or substituted heterocycloalkyl.

In yet another embodiment of the invention the compound has the formula

In another embodiment of the invention wherein the compound has the formula

wherein

Ri is selected from Cl, Br, phenyl, pyridyl or cyano;

R₂ is selected from substituted aralkyl or substituted heterocycloalkyl;

R₃ is selected from substituted alkyl, substituted aryl or substituted heterocyclo;

Zi is selected from CO, S0₂, C0₂, CONHR₅, S0₃, S0₂ NR₅, or C(NCN)NR₅ ; R5 is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl. In one aspect of the inevhtion the compound has the formula

wherein Ri is selected from Cl, Br, phenyl, pyridyl or cyano;

R₂ is selected from substituted aralkyl or substituted heterocycloalkyl;

Zi is selected from CO, S0₂, C0₂, CONHR5, S0₃, SO₂ ?NR₅, or C(NC-N)NR₅;

Prot is triphenylmethyl or Boc; and R₅ is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl. In one aspect the invention provides a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein n is 1; r, s andt are O or 1; p is 0, 1 or 2; V, W and X are selected from the group consisting of oxygen, hydrogen, R¹, R² and R³ ;

O

-C- -

Z and Y are selected from the group consisting of CHR⁹, SO₂, S0₃, CO, C0₂, O, NR¹⁰, SO₂ NR¹¹, CONR¹², or Z may be absent; R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²⁴, R²⁵, R²⁶, R²⁸, R²⁹, R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl;

R⁴ and R⁵ are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R²³ ; U is selected from the group consisting of sulfur, oxygen, ?NR²⁴, CO, SO, S0₂, C0₂,?NR²⁵

C0₂, NR²⁶ CONR²⁷, NR²⁸ S0₂, NR²⁹ S0₂ NR³⁰, S0₂ NR³¹, NR³² CO, CONR³³, P0₂ R³⁴ and P0₃ R³⁵ or U is absent;

R¹, R² and R³ are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl and substituted carbamyl;

R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R¹, R² and R³ may be joined to foim a cycloalkyl group;

^' R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)ρQ wherein Q is • NR³⁶ R³⁷, OR³⁸ or CN; and , - ^"

A, B, C and ?D are carbon;^" with the provisos that V and W are not both oxygen;

W and X together maybe oxygen only if Z is either absent, O, NR¹⁰, CHR⁹, ~N(R¹⁴)- C(0)-, ~N(R¹⁵)~S0₂ -;

R²³ may be hydrogen except when U is SO, S0₂, NR²⁵ C0₂ or KIR²⁸ S0₂ ; and

R⁸ maybe hydrogen except when Z is S0₂,

In one embodiment of the invention the pharmaceutically acceptable salt is mesylate. hi one embodiment of the invention the compound is (R)-7-cyano-2,3,4,5-tetrahydro-l-(lH- imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-lH-l ,4-benzodiazepine, mesylate salt. In yet another embodiment of the innvetion the compound is selected from the group consisting of: 2,3,4,5-Tefrahy(-ho-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

8-Chloro-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-2-methyl-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-4-(l-naph alenylcarbonyl)-l-[[l-(phenylmemyl)-lH-imidazol-5-yl]methyl]- lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-(lH-imidazol-4-yl-methyl)-4-(l-naρhthalenylsulfonyl)-lH-l,4- benzodiazepine, hydrochloride;

(S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l^"-(lH-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H-l,4-benzodiazepine-4- carboxamide, hydrochloride; 2-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)-lH-l,4-benzodiazepin-4- yl]sulfonyl]benzoic acid, methyl ester, hydrochloride; 7-Bromo-2,3 ,4,5 -tetrahydro- 1 -( lH-imidazol-4-ylmethyl)-4-( i -naphthalenylcarbonyl)- 1 H-l ,4- benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenenylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-2-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahy(ho-l-[3-(lH-imidazol-2-yl)ρroρyl]-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[3-Amino-3-(lH-imidazol-2-yl)propyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-3 -methyl-4-(l -napthalenylcarbonyl)- 1 H- 1 ,4- benzodiazepine, hydrochloride;

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetahydro-l-(lH-imidazol-4-ylmethyl)-9-methyl-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-ylmethyl-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-

1 H-l ,4-benzodiazepine, trihydrochloride; l-[[2-Aιrunome yl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tefrahydro-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]acetamide, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-naρhtho[2,3-e]-

1,4-diazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH--b-nidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-8-nitro-lH-l,4- benzodiazepine, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)-8-amino- IH- 1 ,4- benzodiazepine, dihydrochloride;

N-[2,3,4,5Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]benzamide, dihydrochloride; N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride; 2,3,4,5-Tefrahy(ho-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-l^; 4- benzodiazepine, dihydrochloride; ^* "2,3A5-Tefrahydro-l7[2-(lH^iιώdazol-4-^ benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,S-tefrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[[l-(2-Aminoethyl)-lH-imidazol-5-yl]methyl]-2,3,4,5-tetrahydro-4-naphthalenylcarbonyl)-7- phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepme-4-carboxylic acid, phenylmethyl ester; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[2-(trifluoromethoxy)berιzoyl]-lH-

1 ,4-benzodiazepine;

1,2,3 ,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-N-methyl-N,7-diρhenyl-4H- 1 ,4- benzodiazepine-4-carboxamide, dihydrochloride;

2,3,4,5,-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaleneylcarbonyl)-7-(l- piperidinylsulfonyl)-lH- 1,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphmalenylcarbonyl)-7-pyridin-2-yl-lH-

1,4-benzodiazepine, trihydrochloride;

7-(2-Furanyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcabonyl)-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahyά^o-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-(2-thienyl)-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-irmdazol-4-ylme yl)-4-(l-naphthalenylcarbonyl)-7-(4-pyridinyl)-lH-

1,4-benzodiazepine, trihydrochloride; 5 2,3,4,5-Tetrahydro-l-[3-(lH-imidazol-2-yl)ρropyl]-4-(l-naphthalenylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahy(ho-l,4-bis(lH-irm^azol-4-y?-methyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylmethyl)-7-ρhenyl-lH-l,4-0 benzodiazepine, trifluoroacetate;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-methoxy-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahyά^o-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine-7-carboxylic acid, dihydrochloride; 5 2,3 ,4,5-Tetrahydro- 1 -( lH-imidazo -5-ylmethyl)-4-(l -naρhthalenylcarboiιyl)-7-cyclohexyl- 1 H-^:

1,4-benzodiazepine, 2,5 hydrochloride; - -- - - 7-Butyl-2 ,4 5-tefrahy<-ho-l-(,rff-M - -- - benzodiazepine, dihydrochloride;

1 -[ [2-(2-Amino_.ethyl)- 1 H-imidazol-4-yl]methyl] -2,3 ,4,5 -tetrahydro-4-(l -naphthalenylcarbonyl)-0 7-ρhenyl-lH-l,4-benzodiazeρine, trihydrochloride; - l-[[2-(-Aminomemyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tefrahy(ho-4-(l-naphthalenylcarbonyl)-

7-phenyl-lH-l ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naphthalenylcarbonyl)-8-[N,N-bis(phenyl- methyl)amino]-lH-l,4-benzodiazepine, trihydrochloride; 5 N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8yl]phenylsulfonamide, dihydrochloride;

N-Phenyl-2,3,4,5-tehahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzo-diazepine-7carboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4-0 benzodiazepin-8-yl]-3-methylbenzamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- _. benzodiazepin-8-yl]-4-methylbenzamide, dihydrochloride;

3-Chloro-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH- l,4-benzo-diazeρin-8-yl]benzamide, dihydrochloride; 7-Bromo-2,3,4,5,-tefrahydro-l-[[2-[(dimemylamino)-memyl]-lH-imidazol-4-yl]methyl]-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-(4-CUorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, dihydroc-hloride; 7-(3-AiE nophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

1H-1 ,4-benzodiazepine, trihydroc-hloride;

1 -Methyl-N-[2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)- 1H-

1 ,4-benzodiazepin-8-yl]- lH-ρyrrole-2-carboxamide, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-furancarboxamide, dihydroc-hloride;

7-(3-Chlorophenyl)-2,3,4,5-tefrahydro-l-(lH-in-udazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, dihydrochloride;

2-Me l-N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-

1 ,4-benzodiazepin-8-yl]benzamide, dihydrochloride; -- N-Ehenyl-N'-[2,3,4,5-tefr iydro-l-(lH-imidazol-4-y--methyl)-4^(l-riaphthalenylcarbonyI)-IH- - l 4-benzodiazepin-8-yl]urea, dihydrochloride;

2,3,4,5-Tetrahydrό-^'l-(lH-imidazol-4-yta^

1,4-benzodiazepine, trihydrochloride;

2,3 4,5-.Tefrahydro-l-(lH-nnidazol-4-y]methyl)-9-methoxy-4-(l-napbthalenylcarbonyl)-lH-l,4- diazepine, dihydrochloride; - .

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-(phenylmethyl)-

IH- 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-3-(2-hydroxyethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

1 H-l ,4-benzodiazepine, trifluoroacetate;

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

4-Acetyl-7-bromo-2,3,4,5-texrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, hydrochloride;

7-Bromo-l,2,3,5-tetrahydro-l-(lH-imidazol-4ylmethyl)-3-(ρhenylmethyl)-4H-l,4- benzodiazepine-4-carboxamide, trifluoroacetate;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-

1H-1 ,4-benzodiazepine, hydrochloride; 4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate;

4-Acetyl-7-bromo-3-[(4-clιlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)- lH-l,4-benzodiazepine, dihydrochloride; 5 4-Acetyl-2,3,4,5-tefrahycho-l-(lH-imidazol-4-ylmethyl)-3-(?phenylmethyl)-lH-naphtho[2,3-e]-

1,4-diazepine, monohydrochloride;

N-Cyclohexyl-N'-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl]-

1H-1 ,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-iιnidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-lH-0 naphtho [2,3 -e]- 1,4-diazepine, monohydrochloride;

2,2-Dimethyl-N-[2,3,4,5-tefrahydro-l-(lH-i^

1H-1 ,4-benzodiazeρin-8-yl]propanamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-ύnidazol-4-ylmethyl)-4-(l-naphthalenylsulfonyl)-7-phenyl-lH-l,4- benzodiazepine, monohydrochloride; 5 4-Acetyl-7-bromb-2;-3,4,5-tefrahydro-l-(lH-imidazol-4÷ylmethyl)-3-(2-naphthalenylmethyl)-- _;~

1H- 1,4-benzodiazepine, dihydrochloride; ' - ^• -^•.

4VAcetyl~7 >romόi2;3,4,5-tefrahydrø-^^

1 H-l ,4-benzodiazepine, dihydrochloride; - -7-(2-Chlorophenyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naρhthalenylcarbonyB- ,.0 lH-l,4-benzodiazepine, dihydrochloride;-

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazepine, monohydrochloride; . l-Methyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-

1 ,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, trihydrochloride; 5 N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-4-moφholinecarboxamide, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4- benzodiazepin-8-yl]-3-methylbutanamide, dihydrochloride; l,2,3,5-Tefrahydro-l-(lH-irm^azol-4-ylmethyl)-N,N,7-triphenyl-4H-l,4-benzodiazepin -0 carboxamide, dihydrochloride; l,2,3,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-naρhtho[2,3-e]-l,4- diazepine-4carboxylic acid, methyl ester, monohydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(4-ρhenyl-l,2,3-thiadiazol-5- yl)carbonyl]-lH-l ,4-benzodiazepine, trifluoroacetate; 8-[[(Cyclohexylammo)carbonyl]amino]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxylic acid,l,l-dimethylethyl ester;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3-

(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxylic acid, 1,1-dimethylethylester; 7-Bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-5H-l,4- benzodiazepin-5-one, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[l-oxo-3-(l-piperidinyl)propyl]-7-phenyl-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1 ,4- benzodiazepine, trihydrochloride;

4-[(5-Bromo-3-pyridinyl)c--urbonyl]-2,3,4,5-tefrahydro-l-(lH-iαιidazol-4-ylmethyl)-7-phenyl-

1 H-l ,4-benzodiazepine, trihydrochloride;

(S)-4-[2-(Dimethylamino)- 1 -oxo-3 -phenylpropyl] -2,3 ,4,5-tetrahydro- 1 -(1 H-imidazol-4- ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride; ■ 2,3,4,5-Tefrahydro-4-[4-hydrcxy-3-(4-moφholinyl-methyl)behzoyl]-l^lH-iϊi7idazo 4-_'-.- ylmethyl)-7-phenyl-lH- 1,4-benzodiazepine, trihydrochloride; ^• -" -

(S)~2,3,4,5-Tetrahydro-l -(lH-imidazol-4-ylme yl)-4-[-(r-methyl~2-pyι oli inyl)carbonyl3--77? - phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y--me yl)-7-phenyl-4-[[2-(propylt-hio)-3- <.. , , pyridinyl]carbonyl]-lH-l,4-benzodiazepine, trihydrochloride;

4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[[2-(phenylthio)-3- pyridinyl]carbonyl]-lH-l,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3- piperidinyl] carbonyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-memoxy-3-pyridinyl)carbonyl]-7-phenyl-

1H-1 ,4-benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-phenyl-4- [(5-phenyl-4-oxazolyl)carbonyl] - IH- 1,4-benzodiazepine, dihydrochloride;

4-Acetyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y?-memyl)-7-phenyl-4-[(tetrahydro-3-furanyl)carbonyl]-

1H-1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahycho-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-(4-moφholinylmethyl)benzoyl]-7

2,3,4,5-Tefrahycfro-l-(lH-imidazol-4-ylmemyl)-4-^ 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y-hnethyl)-4-[l-oxo-3-(phenylsulfonyl)propyl]-7-phenyl-

1H-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(3-pyridinylacetyl)-lH- l,4benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

2,3₃4₅5-Tefrahydro-l-(lH-imidazol-4-yhnethyl)- 4-(4-isoquinolinylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, trihydrochloride; 4-[(2-^'Chloro-3-pyridinyl)carbonyl]-2,3,4,5 :ettώydro-l-(lH-imidazol-4-ylm.ethyl)-7-phenyl-

1H- 1,4-benzodiazepine, trihydrochloride; . ^{"" .} -^•■-. - " 2,3 i ^Tefrahydro-r-(lH-imidazol-4-ytø^ --• - benzodiazepine, trihydrochloride;

4-[(2,6-pimethoxy-3-pyridinyl)carboRyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yltnethyl)-7- - .phenyl-lH-lAbenzo-diazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

4-(2-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-[3-(Dimemylammo)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(l-phenylcyclopropyl)carbonyl]-

1H- 1 ,4-benzodiazepine, dihydrochloride;

4-[(Bicyclo[4.2. 0]octa-l,3,5-trien-7-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH- 1,4-benzodiazepine, dihydrochloride;

4-Benzoyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-(2-Chlorobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(2,3-Dic orobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

N-[2-[[2,3,4,5-Tefrahydro-l-(lH--h-mdazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepin-4- yl] carbonyl]phenyl] acetamide, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; . 4-(2,3-Dime oxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,4-Dimethoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-in-ύdazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; ..-. 4-(2,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(2,6-Dimemoxybenzoyl)-2,3,4,5-tet^^ • benzodiazepine, dihydrochloride; - .^r :4-(2,3-Dihydroxyberiz-oyl)-2,3,4,-5- etrahyd - benzodiazepine, dihydrochloride;

4 ([l,r-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmftLhyl 7-ρhenyl-lH- 1,4-benzodiazepine, dihydrochloride; • -

2,3,4,5Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4 2,3-Dimethylbenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(3-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3-Chlorobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3 ,4-Dimethoxybenzoyl)-2,3 ,4, 5-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-ρhenyl- 1 H- 1 ,4- benzodiazepine, dihydrochloride; 4-(3,5-Dimethoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydroc-hloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(l,2-Dioxo-2-ρhenylethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[(2-Ethoxy-l-naρhthalenyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydroc-hloride;

4-(Fluorophenylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(Diphenylacetyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-4-(2-hydrόxy^ -oxo-2-phenylpropyl)-l-(lH-imidazoi-4-y?hnethyl)-7-ph^ lH-l,4-benzodiazepine, dihydrochloride; ^• - ^•

2,3 ,4,5-Tetrahydro- 1 -(lH-iHUdazol-4sylmethyl)-4-(lH-iι dol-2-ylcarbonyl)-7-phei3yi- 1 H- ϊfi- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-3-ylcaι onyl)-7-phenyl-lH-l,4- . benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-5-ylcarbonyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol,4-ylmethyl)-4-[(l-methyl-lH-indol-2-yl)carbonyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 4-(2-Benzofuranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(3 -pyridinylcarbonyl)- IH- 1 ,4- benzodiazepine, N-oxide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-7-phenyl-4-(2-ρyridinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(l-isoquinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 4-(3-CMoro-2-mfrobenzoyl)-2,3,4,5-tefrahy(ho-l-(lH--hmdazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-nitrobenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxy-2-mtrobenzoyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-4-ylcarbonyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[(2,6Dihydroxy-3-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-(lH-Ber--zin-udazol-5-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepine, trihydrochloride;

4-(lH-Benzofriazol-5-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7"phenyl-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4^ phenyl- 1 H- 1 ,4-benzodiazepine trihydrochloride;

N-[3-[[2 3.,4,5-Tefrahyαrorl-(lH-imidazo^ yl] carbonyl]phenyl] -acetamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oχo_-2-phenylpropyl)-7-phenyl- 1H~1 ,4-benzodiazepine, dihydrochloride;

4-[2-( imemylamino)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1 ,4-benzodiazepine, trihydrochloride; - 4-(3-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine,dihydrochloride; 2,3,4,5-Tetrahydro-4-(2-hydroxy[l,r-biphenyl]-3-ylcarbonyl)-l-(lH-imidazol-4-ylmethyl)-7- phenyl-1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-

1H-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahy(-ho-l-(lH-i-t dazol-4-y?-methyl)-4-[(2-methoxy-l-naphthalenyl)carbonyl]-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-[(2-hydroxy-4-qiunolinyl)-carbonyl]-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2-[[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazeρin-4- yl] carbonyl]benzamide, dihydrochloride; N-(l,l-Dimethyle l)-2-[[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl]carbonyl]benzamide, dihydrochloride;

N-(4-Fluorophenyl)-N'-[3-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl]carbonyl]phenyl]urea, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y-hnemyl)-4-[(3-methyl-4-oxo-2-phenyl-4H-benzopyran-

8-yl)carbonyl]-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y-hnethyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]-lH-

1,4-benzodiazepine, dihydrochloride;

4-(2-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine,dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[[(4- methophenyl)sulfonyl] amino]benzoyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(6-qumolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 2,3,4;5-fefr dro-l-(lH-imid^ol-4-yhftethyl)-7-ρHenyl-4-(8-quin^'όlinylcarbonyl)-lH^ benzodiazepine, trihydrochloride;

4-(Ben2o[b]tbiophen-2-ylc;tfM

IH- 1,4-benzodiazepine, dihydrochloride;

4-[[4-(Dimethylamino)-l-naphthalenyl]-carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH- 1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmemyl)-7-phenyl-4-(lH-purin-6-ylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methoxyphenyiacetyl)-7-phenyl-lH^l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(5-methyl-l-phenyl-lH-pyrazol-4- yl)carbonyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine,trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)-l-oxoρropyl]-7-phenyl- lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-4-phenyl-2H-ρyran-4- yl)carbonyl]- IH- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(methylphenylamino)benzoyl]-7-phenyl-

1H-1 ,4-benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4quinolinylcarbonyl)- 1 H-phenyl-

1H-1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)-lH-l,4- benzodiazepine, N-oxide, dihydrochloride;

N-Methyl-N-(2-pyridinylmethyl)-2-[[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepin-4-yl]carbonyl]benzamide, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-isoqumolinylcarbonyl)-7-ρhenyl-lH-l,4- bezodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-naphthalenylthio)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

4-[3-(3,4-D-hnethoxyphenyl)-l-oxopropyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-lH- 1 ,4-benzodiazepine, trifluoroacetate (1 :2);

4-([l,r-Biphenyl]-4-ylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylacetyl)-lH-l,4- benzodiazepine,trifluoroacetate (1:2); 4-([l,r-Biphenyl]-2-ylcarbonyl)^3,4,5-tefrahydro-l-(lH-imidazor-4-ylmethyl)-lH-l,4- ^{' "} - benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)^4-[(2-phenyl-4-quinolinyl)carbonyl]" H-l,4-- benzodiazepine, trifluoroacetate (1:3);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)~4-(3-ρyrid trifluoroacetate (l:-3); <

(S)-4-[2-(Dimethylamino)-l-oxo-3-phenylpropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:3); (S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-oxo-4-phenyl-^'3-oxazolidinyl)acetyl]- lH-l,4-benzodiazepine, trifluoroacetate (1:2);

4-(9- Acridinylcarbonyl)-2,3 ,4, 5-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate (1:3);

2,3,4,5-Tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-lH-l,4-benzodiazeρine, trifluoroacetate (1 :2);

2,3 ,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-[[4^,-(trifluoromethyl)[ 1 , 1 '-biphenyl]-2- yl]carbonyl]-lH-l,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)-lH-l,4-benzodiazepine, trifluoroacetate (1 :2); 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyI)-4-(2-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxo-4-phenylbutyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2); 2,3,4,5-Tefrahydro-l-(lH-i-midazol-4-ylmethyl)-4-[(2-ρhenoxyρhenyl)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]-lH-

1 ,4-benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y-b-nemyl)-4-[2-[(phenylmethyl)amino]benzoyl]-lH-l,4- benzodiazepine, trifluoroacetate (1:3); l,2,3,5-Tefrahy(ho-l-(lH--unidazol-4yl-methyl)-N,N-diρhenyl-4H-l,4-benzodiazeρine-

4carboxamide, hydrochloride;

1 ,2,3,5-Tetrahydro- 1 -(lH-imidazol-4-yl-methyl)-a,7-diphenyl-4H- 1 ,4-benzodiazepine-4-acetic acid, methyl ester, hydrochloride; 4-Acetyl-2,3,4,5-tefrahydrό--l-(lH-inddazol-4-ylmethyl)-3-(pheπylmethyl)-lH-l,4- benzodiazepine, hydrochloride; - (R)-7-Bromo-2,3A5-tefrahydro-l-(lH-^^ ^•-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(TR.)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmemyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH- l,4-benzodiazepine-7-carbonitrile, monohydrochloride;

(R)-4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(ρhenylmethyl)-lH-

1,4-benzodiazepine, monohydrochloride;

7-Bromo-4-[[2-(dimethylamino)ethyl] sulfonyl] -2,3 ,4,5-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-

3-(phenylmethyl)-4H-l,4-benzodiazepine, trifluoroacetate (1:2); 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(l,2,3,4-tetrahydro-l- quinolinyl)carbonyl] - 1 H- 1 ,4-benzodiazepine, monohydrochloride;

N-Ethyl- 1 ,2,3 ,5-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-N,7-diphenyl-4H- 1 ,4-benzodiazepine-

4-carboxamide, monohydrochloride;

4-[(2,3-Dihydro-lH-indol-l-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride;

(R)-4-[[2-(Dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1); [2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, dihydrochloride;

(^)-7-Bromo-2,3,4,5-tefrahy(ho-l-(l-methyl-lH-imidazol-5-yl)methyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-b enzodiazepine, hydrochloride; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

4-[2-(4-Chloroρhenyl)-l,2-αιoxoethy]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-

1H-1 ,4-benzodiazepine, hydrochloride;

4-(l,2-Dioxopropyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tefrahy(ho-l-(lH-imidazol-4-ylme yl)-4-[2-(4-mtrophenyl)-l,2-dioxoethyl]-7-phenyl- lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(4-methoxyphenyl)-l,2-dioxoethyl]-7- phenyl-lH-l,4-benzodiazepine, hydrochloride; 2,3,4^5-Tefrahydro-l-(lH-imidaz61-4-ylmethyl)-7-phenyl-4-^'(-3,3,3-trifluoro-l,2-dioxopropyl)- ^:" lH-l,4-benzodiazepine, trifluoroacetate (1 :2);

(R)-7-Bromo-2,3,4,54efrahydrΘ-l-(l^

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(2-lH-imidazol-4-ylethyl)-4-(methylsulfonyl)-3- (phenylmethyl)- IH- 1,4-benzodiazepine, monohydrochloride; ^■

8-[(Cyclohexylcarbonyl)ammo]-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-4H-l,4-benzodiazepine-4-carboxyhc acid, methyl ester, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-l-piperidinecarboxamide, dihydrochloride; (R)-7-Cyano-l,2,3,5-tefrahyάro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxylic acid, ethyl ester, hydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-lH-

1 ,4-benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-4H-l,4-benzodiazepine, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)-lH-l,4- benzodiazepm8-yl]cyclohexanecarboxamide, dihydrochloride; 8-[(Cyclohexylcarbonyl)armno]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N-phenyl-lH- l,4-ben-zodiazeρine-4-carboxamide, dihydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride; N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]-lH-l,4- benzodiazepin-8-yl] cyclohexanamide, dihydroc-hloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride;

(3R)-7-Bromo-l-[cyano(lH-imidazol-4-yl)memyl]-2,3,4,5-tetrahy(ho-4-(memylsulfonyl)-3- (phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(3R)-l-[2-Amino-l-(lH-imidazol-4-yl)emyl]-2,3,4,5-tefrahydro4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-(Dimemylan-uno)-l-(lH-imidazol-4-yl)ethyl]-2,3,4,5-tefrahydro-4-(methylsulfonyl)-

3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride; (3R)-l-[2-Amino-l -(lH-imMazol-4^yl)emyl]-7-bromo-2,3,4,5-tefrahydro-4-(methylsulfonyϊ)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l--[2-(Dirne lamino)-l-(lH.imidazol-4-yl)e yl]--7-bromo-2,3,4,5-tefrahyto

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Cyano-l,3,4,5-tefrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-3-(phenylmethyl)-4- (ρhenylsulfonyl)-2H-l,4-benzodiazepin-2-one, monohydrochloride;

7-Cyano- 1 ,3 ,4,5-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(phenylsufonyl)-

2H-1 ,4-benzodiazepin-2-one, monohydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(memylsulfonyl)-3-(2-phenylethyl)-

1 H-l ,4-benzodiazepine, dihydrochloride; 7-Bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(S)-7-Bromo-3-(cyclohexylmethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-methoxyphenyl)methyl]-4-

(methylsulfonyl)- IH- 1 ,4-benzodiazepine, dihydrochloride; 4-Acetyl-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)- lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-7-bromo-3-[(3-chlorophenyl)memyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-

1H-1 ,4-benzodiazepine, dihydrochloride; 5 7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-hydroxyphenyl)methyl]-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-8-(hydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- 10 lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-

(phenoxymethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

N-Cyclohexyl-2,3,4,5τtetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-

1 ,4-benzodiazepine-8-carboxamide, dihydrochloride; 15 N-(Cyclohexylmethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmetlϊyl)-4-(l, naphthalenylcarbonyl)-lH-l,4-benzodiazepine-8-carboxamide, dihydϊOchloride; ■ - - - 2,3,4,5-Tefrahydro --(lH-imid^ol-4-ylme^

1H-1 ,4-benzodiazepine-8-carboxamide, dihydrochloride;

(R)-4-Acetyl-7-[2-[(dimemylamino)methyl]phenyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- 20 ylmethyl)-3-(phenylmethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(R)-4-Acetyl-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, monohydrochloride; . ÷

(^)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxobutyl)-3-(phenylmethyl)-

1H-1 ,4-benzodiazepine, monohydrochloride; 25 (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxopropyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- pyridinylacetyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- 30 thienylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methylethyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

[(trifluoromethyl)sulfonyl]-lH-l,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tetrahy(ho-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(^)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride; (R)-2,3,4,5-Tetrahydro-l-(lH-irnidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(^)-7-Cyano-4-[(4-fluoroρhenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-4-[(3-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylme yl)-4-[(l.-memyl-lH-imidazol-2- yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-4-[^'(3-Brbmophenyl)sulfonyl]-7cyano-2,3,4,5-tetrahy<ho-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH- 1,4-benzodiazepine, monohydrochloride;

(R)^N-[5-[[7-cyano-2,3,4,5-tefrahydro--l-.(lH-imidazol-4-yteethyl)^"-3. henylmethyi -lH-l-,4- benzodiazepin-4-yl]sulfonyl]-4-methyl-2-thiazolyl]acetamide, dihydrochloride;

4-Acetyl-2,3,4,5-tefral- dro-l-(lH-imidazol-4- ylmemyl)-3-(phenylmethyl)-7-(4-py^ 1,4-benzodiazepine, trihydrochloride; - - .

2,3,4,5-Tefrahycho-l-(lH- nidazol-4-y]methyl)-4-(2-phenyl-l,2-dioxoethyl)-7-(4-pyridinyl)- lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-

(trifluoromethoxy)benzoyl] - 1 H- 1 ,4-benzodiazepine, trihydrochloride; (R)-2,3,4,5-Tetrahydro-l -[(1 -methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7-ρhenyl-3-

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylacetyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

4-(2-Benzothiazolyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-irnidazol-4-ylmethyl)-3-(ρhenylmethyl)-7-(3-ρyridinyl)-4-

(trifluoroacetyl)-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride; 7-Bromo-3-[(l,l-dimemylethoxy)me l]-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-5H-

1 ,4-benzodiazepin-5one;

7-Bromo-2,3,4,5-tefrahycho-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenoxymethyl)-lH-l,4-benzodiazepine, dihydrochloride; 7-Bromo-2,3,4,5-tefrahy(ho-3-(hydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-3-[(l,l-dimethyle oxy)methyl]-2,3,4,5-tefrahyάro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester, trihydrochloride;

[4-Acetyl-7-bromo-2,3 ,4,5-tetrahydro- 1 -( lH-imidazol-4-ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4- benzodiazeρin-8-yl]carbamic acid, 2-methylpropyl ester;

N-[4 Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride; [7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yln ethyl)-4-(methylsulfonyl)-3-(phenylnιethyl)- lH- ,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester; (R)-2,3A,5-Tetrahydfo-l-(lH midazol-4-ylmethyi)-4-(phenylsulfoi}yl)-3- phenylmethyl)-lH-- l,4-benzodiazepine-7-carbonitrile, monohydrochloride;

7-Bromo-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4-. - benzodiazepine-4-acetamide; >

7-Bromo-4-[(dimethylamino)acetyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H- 1 ,4-behzodiazepine;

(R)-7-Bromo-4-(l,2-dioxopropyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; (R)-7-Bromo-4-(cyclopropylcarbonyl)-2,3 ,4,5-tetrahydro- 1 -( lH-imidazol-4-ylmethyl)-3 -

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate;

(TR)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l,4-bis(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, dihydrochloride;

7-Bromo-l,2,3,5-teteahy(ho-l-(lH-imidazol-4-y-lmethyl)-N_JN-dimethyl-3-(phenylmethyl)-4H- l,4-benzodiazepine-4-sulfonamide, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepine-7-carbonitrile, monohydrochloride; (R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-in-udazol-4-yta^

4H- 1 ,4-benzodiazepine-4-carboxamide monohydrochloride;

N,N-Diethyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- henylmethyl)-lH-l,4-benzodiazepine-7-carboxamide, monohydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(l-ρhenyl-lH-tetrazol-5-yl)-lH-l,4- benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-4-(2- pyrazinylcarbonyl)-4H-l ,4-benzodiazepine, monohydrochloride;

(R)-4-[7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepin-4-yl]-4-oxobutanoic acid, methyl ester, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-moφholinocarbonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[[2-(l- pyrrolidinyl)ethyl]sulfonyl]-lH-l ,4-benzodiazepine, dihydrochloride; (S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phen3q-3-(3- - pyridinylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-irm^azol-4-ylmethyl)-7-phenyl-3-(3-ρyridinylmethyl)-4- 2- - thienylsulfonyl)- 1 H-l ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(proρylsulfonyl)-3-(3- pyridinylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- pyridinylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; -

2,3,4,5-Tetrahydro-l-(lH-imidazoh4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7-(2- pyrimidinyl)- 1 H- 1 ,4-benzodiazepine,dihydrochloride; (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

[(trifluoromethyl)sulfonyl]-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4-

(trifluoroacetyl)-lH-l,4-benzodiazepme, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-7-(4-pyridinyl)-4-(2- thienylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydrol-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(ρhenylsufonyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, dihydrochloride; (^)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-( henylmethyl)-4-(ρropylsulfonyl)-7-(4- pyridinyl-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-(phenylmethyl)-4-[(3,5- dimethyl-isoxazol-4-yl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Cyano4[(4-cyanophenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahyώo-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2,2,2- trifluoroethyl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(R)-[(5-Bromo-2-tm^nyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-methoxyphenyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

N-[[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-lH-l,4- benzodiazepin-3-ylmethyl]benzamide, dihydrochloride; (R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylιnethyl)-

4H-1 ,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydfo-N,N-dimethyl-l-[(-l-methyl-lH-imidazol-^5-yl)methyl]-3-

(ρheny?lmemyl)-4H-l,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7-Cmoro-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol- -yl)methyl]-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(ρhenylsulfonyl)-3- phenylmethyl)-lH- 1 ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, tetrahydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-lH-imidazol-4- yl)sulfonyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(l-methyl-imidazol-5-ylmethyl)-4-[(2-moφholin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-moφholin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Chloro-4-[(dimethylan-ύno)sulfonyl]-l-[(l-memyl-lH-imidazol-5-yl)methyl]-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-7-CMoro-2,3,4,5-tefrahydro-l-(l-methyl-hnidazol-5-ylmemyl)-4-[(4-methyl-piperidin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-2,3,4,5-tefrahydro-l-(l-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxylic acid, isopropyl ester, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-4-[[2-(lH-imidazol-l-yl)ethyl]sulfonyl]-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-i-midazol-4-ylmethyl)-4-(ρroρylsulfonyl)-3-(3- pyridinylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

7-Bromo-2,3,4,5.-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-5-one, hydrochloride; - (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-l-ylacetyl>4-(methylsulfenyl)-3- :

(phenylmethyl)-lH-l-,4-benzodiazepine, trifluoroacetate; l,2,4,5-Tefrahydro-l-(lH midazol-4-yimethyl)-2-(2-phenylethyl)-3H-l,4-behzodiazφin--3-oae;

2;3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-(2-ρhenylethyl)-lH-l,4- benzodiazepine, monohydrochloride; .. . . (R)-2,3,4,5-Tetrahydro-l lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(4- pyridinylmethyl)-lH-l,4-benzodiazepine, dihydrocWoride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)-lH- l,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H- 1 ,4-benzodiazepine-4-carboxamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(l-(4cyanopheny?lmethyl)-imidazol-5ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine-7-carbonitrile, hydrochloride; (R)-2,3,4,5-Tetrahydro-l-(l-(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4-(methylsulfonyl)-

3phenylmethyl)- IH- 1 ,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-4-Benzoyl-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-me l-lH-imidazol-5-yl)memyl]-3-(pyridin-3-ylmethyl)- 4-(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; (TR)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)me yl]-3-(pyridin-3-ylmethyl)-

4-(propylsulfonyl)-lH-l ,4-benzodiazepine, trihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(lH-mιidazol-4-yl)memyl]-3-(pyridin-3-ylmethyl)-4^

(phenylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-in-ύdazol-4-y?hnemyl)-4-(me lsulfonyl)-7-ρhenyl-3-(phe

1H-1 ,4-benzodiazepine; l,2,3,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-N-(l-naphthalenyl)-7-ρhenyl-4H-l,4- benzodiazepine-4-carboxamide, monohydrochloride;

(S)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-y]methyl)-4-(2,3-dimethylbenzoyl)-lH-l,4- benzodiazepin-8-yl] cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-N-[2-(dimethylamino)emyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N- methyl-3-(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxamide₅ trifluoroacetate (1 :2); 7_TBromo-2,3,4,5--tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; <R)-7-Cyano-4-(^furanylcarbonyl)-^ .

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1); ( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-i idazol-4-y-hnethyl)-4-[(4-mtrophenyl)sulfonyl]-3- (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; . ^■ -.: . ■ .

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[4-(4-methyl-l- piperazin)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[(4- dimethylammo)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; (^)-7-Bromo-4-[[2-(dimethylamino)e yl]sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(3- pyridinylsulfonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(me ylsulfonyl)-3-(phenylmethyl)-lH-l,4- benzo-diazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-[(l-me yl-lH-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-4-[[3-(Dimethylamino)proρyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tefrahyto-l-(lH-imidazol-4-y?hnethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride;

4-Butyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-[E2-(4- moφholmyl)e yl]sulfonyl]-3- henylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-l-(lH-imidazol-4-ylmethyl)-4-(4-moφholinylsulfonyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, monohydrochloride;

(R)-7-Cyano-l-[(l-memyl-lH-imidazol-5-yl)methyl]-4-[(4-moφholinyl)sulfonyl-]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-aminophenyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; '- 2,3,4,5-Tefrahycho -(lH-imidazol-4-ylmethyl)-4-[(4-ρyridylthio)acetyl]-7-ρhenyl-lH-lVl~^{" r} benzodiazepine, dihydrochloride; " N-(4-CUoroρhenyl)-N'-cyano-l,2,3,5-tetfahyά o-ϊ-(lH-imidazol-4-ylmethyl)-7-phenyl-4H-l,4-- benzodiazepine-4-imidamidei^jmonohydrochloride;

4-Acetyl-7-bromo-l,2,4,5, ,3'-hexahydro-l-(lH-imidazol-4-ylmethyl)spiro[3H-l,4- benzodiazepine-3,2'-[2H]indene], dihydrochloride; ' -

7-Bromo-4-[3-(dimethylamino)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1);

(^)-2,3,4,5-Tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-(phenylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride; 2,3,4,5-Tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-phenyl-3-

(pyridin-3-yl-methyl)-lH- 1,4-benzodiazepine, hydrochloride (1:1.5), trifluoroacetate (1:0.75) salt;

4-[4-(Fluorophenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-2-(2-phenylethyl)-

1 H-l ,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-[[2-(l- moφholinyl)ethyl] sulfonyl] -3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(4- bromophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(memyl-sulfonyl)-3-(thiazol-4- ylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(propyl-sulfonyl)-3-(thiazol-4- ylmethyl)-lH-l,4-benzodiazepine, hydrochloride; 5 (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(propylsulfonyl)-3-(4- bromophenylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, trihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-l-me yl-imidazol-5-ylmethyl)-3-(pyridin-3-ylmethyl)- 10 4-(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4- cyanophenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydroc-hloride;

(^)-7-Cyano-4-[(N-methyl-N-phenylmemyl)ammosulfonyl]-l-[(lH-imidazol-4-yl)methyl] 3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride; IS.. (R)-7-Cyano4-[N-(tefrahydroisoquinoline)sulfonyl]-l-[(lH-imidazol-4-yl)metiιyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; -• '

(R)-7-Cymo-2,3,4,5-tetrahydro- --(lH midazor-4-ylmethyl)-4-(phenylsulfonyl)-3-(2- - ^" thienylmethyl)-lH- 1,4-benzodiazepine, hydrochloride; cis-2,3,4,5-Tetrahydrorl,5-bis(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,5- 20 benzodiazepine-2-carboxylic acid ethyl ester-trifluoroacetate (1:2);

(R)-7-Cyano4-[(N-piperidinyl)sulfonyl]-l-[(lH-imidazol-4-yl)memyl]-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-l-me yl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-(2-. thienylsulfonyl)-lH-l,4-benzodiazepine, hydrochloride; 25 (R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4-[[2-

(dimethyla-mino)ethyl]sulfonyl]-lH-l,4-benzodiazeρine, trihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-l-memyl-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, hydrochloride;

N-(Cyano)-N"-methyl-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4H-l,4- 30 benzodiazepine-4-imidamide, hydrochloride;

(R)-7-Cyano-4-[(2-nitrophenyl)-sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyl-methyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(4-methyl-ρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H-l ,4-benzodiazepine, hydrochloride; (R)-7-Cyano4-(butylsulfonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-

1H-1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-trifluoro-memylphenyl)sulfonyl]-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-trifluoromethylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-methoxy-carbonylρhenyl)sulfonyl]-2,3,4,5-tefrahycko-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(((4- methylnonyl)-phenyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4- trifluoromethyl)-ρhenyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-.2,3,4,5-tetrahydro-l-(l^:H-imidazol-4-ylmethyl)-3-(phenylmethyI)-4-((3- - methoxypropyl)-sulfonyl)- IH- 1 ,4-benzodiazepine; -(R)-7-Cyano-2,3,4,5-tetrahydro-l»(ffl-imidazol-4-ylmetb l)-3-(phenylmethyl)- -((3,4~ ^" dimethoxyphenyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano_?-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((4-fluorophenyl)methyl)-4- (phenylsulfonyl)-lH-l,4-benzodiazepine; ^'. ^• •

(R)-7-Cyano-4-(N-cyclopropylmemyl-N-propyl)-aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-

3-(phenylmethyl)-lH-l,4-benzodiazepine; -

(R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]-l-[(lH midazol-4-yl)methyl]-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Chloro-4-(methanesulfonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H-pyrido[3 ,4-e]- 1 ,4-diazepine; l,2,3,4-Tefrahydro-7-bromo-4-[(lH-imidazol-4-yl)methyl]-2-phenylmethyl-l-

(methylsulfonyl)quinoxaline;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((imidazol-4- yl)methylsulfonyl)-l H-l ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahy(-ho-l-(lH-imidazol-4-y--methyl)-3-((2-thienyl)methyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-((2- thienyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahy(ho-l-(lH-imidazol-4-ylmemyl)-3-(ρhenylmethyl)-4-((3- methylthioρropyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(((3- methylthioxo)-propyl)-sulfonyl)- 1 H- 1 ,4-b enzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahyαjo-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylsulfonyl)-propyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- methylpropyl)-sulfonyl)-lH-l,4-benzodiazepme;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH--huidazol-4-ylmethyl)-3-(ρhenylmethyl)-4- (cyclopentylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4,4,4- trifluorobutyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

((phenylmethyl)-sulfonyl)-rH-l,4-benzodiazepine; (R)-7-Cyano-2?3,4,5-tefrahydro-l-(lH-imidazo^ benzoyl)-aminomethyl)-thienyl]-sulfonyl]-lH-l,4-behzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahy(fro-l-(lH^ chloro-5-me yl-pyridin-2-yl))-pyrrolyl]-sulfonyl]-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-[((3-methyl- - l,2,4-oxadiazol-5-yl)-phenyl)-sulfonyl]-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-iιnidazol-4-yhnethyl)-3-(phenylmethyl)-4-((2,5- dimethoxyphenyl)-sulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-(N,N-bis-[l-(2-methylpropyl)amino]-sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

)phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-[(N-me yl-N-phenyl)aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3- (phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(2-(2,6-dimethylphenyl)-ethyl)-

4-(methylsulfonyl)-lH-l,4-benzodiazeρine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(l-(N-phthalimidoethyl)-imidazol-5-ylmethyl)-3-

(phenylmethyl)-4-methylsulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-(N,N-dime1hylamino)-ethyl)-imidazol-5-y (phenylmethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-ammoethyl)-imidazol-5-ylmethyl]-3-(ρhenylmethyl)-4- (methylsulfonyl)-lH-l,4-benzodiazepine; (R)-7-Bromo-4-(methanesulfonyl)-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-ylmethyl)-3- ^■ (phenylmethyl)-lH-thieno[2,3-e]-l,4-diazepine;

(R)-7-Bromo-4-(methanesulfonyl)-2,3 ,4, 5 -tetrahydro- 1 -[(1 H-imidazol-4-ylmethyl)-3 - (phenylmethyl)-lH-thieno[3,2-e]-l,4-diazepine;

(R)-4-(me&anesulfonyl)-2,3,4,5-tefrahy⁽-fro-H 8-oxo-ρyrimidino[4,5-e]-l,4-diazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-inύdazol-4-ylmemyl)-3-((4-(2-methoxyethoxy)- phenyl)methyl)-4-(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-y--methyl)-3-((4-(2-(dimethylamin.o)-ethoxy)- phenyl)methyl)-4-(phenylsulfonyl)-lH-l,4-benzodiazepine; ^• ' (R)-7-Cyano--2_?3,4,5-tefrahydro-l-(lH-imM^ ^{' •}--

(methylsulfonyl)- IH- 1,4-benzodiazepine; ^~

(R)~7-Cyaho _^ "2,3,4,5-tefrahydro-r-(lH-imidazol-4-ylsulf(fnyl)-3-(phenylme )4)."4- ..

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahyαro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4- « - (phenylsulfonyl)τlH- 1,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4ylmethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4-

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-ρhenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(propysufonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetτahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-ρhenyl-ethyl]-4- (phenylsulfonyl)-lH-l,4-benzodiazeρine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-ρhenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro4-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-

(methylsulfonyl)-lH-l,4-benzodiazepine; "^""7-Cyano-2,3₅4,5 efrahydro-l H-imidazol-4-ylmethyl)-3-(S)-[(S)-l-ρhenyl-ethyl]-4- ^{~ "}.^'

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine; - .- 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-t-ρherϊyl-e l]^^ -.

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l (lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH- 1,4-benzodiazepine; - . .

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcycloproρyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;.

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- proρylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-( )-[(R)-phenylcyclopropyl)-4- phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-ρhenylcycloρroρyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcycloproρyl)-4- propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH--b-nidazol-4-ylmemyl)-3-(R)-[(S)-phenylcycloproρyl)-4-((2- thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(methylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcycloproρyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-phen3dcyclopropyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetfaEydro-l-(lH-imidazol-4-ylmethyl)-3,-(S)-[(S)-phenylcyclopropyl)-4-

(phenylsulfonyl)-lH-l;4-benzodiazepine; -

•- 7-Gysιιo-2,3,4,54efr ιydr5-l-(lH-i-α^ thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)^3-(phenylmethyl)-4-[(2-(5- ( yridin-2-yl))-thienyl)-sulfonyl])-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5-(-l,2- isoxazol-3-yl))-t?hienyl)-sulfonyl])-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(ρhenylmethyl)-4-

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine; (U)-7-Cyano-2,3,4,5-tefrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρroρyl)-3-(ρhenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

.(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρropyl)-3-(ρhenylmethyl)-4-((2- thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(ρhenylmethyl-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahy(ho-l-(2-(lH-iι dazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)ethylsulfonyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH---midazol-4-ylmethyl)-3-(jphenylmethyl)-4-((l-o^ amino)-l H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(methanesulfonylamino)-lH- 1,4-benzodiazepine; and

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonylamino)-lH-l,4-benzodiazepine.

In one aspect of the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein Ri is Cl, Br, CN, optionally substituted phenyl, or optionally substituted 2-,3- or 4-pyridyl; R₂ is optionally substituted lower alkyl, or optionally substituted aralkyl; R₃ and R₅ are each independently optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heterocyclo; R_t is hydrogen or lower alkyl; Zi is CO, S0₂, C0₂ or S0₂ N(R₅)-; and n is 1 or 2. In one embodiment the compound of the invention has the following substituents:

Ri is Br, or CN;

R₂ is optionally substituted benzyl;

R₃ is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted

2-thienyl, or optionally substituted 1-piperidinyl; I _t is hydrogen, or methyl;

Zi is CO, S0₂, or S0₂ N(R₅)-;

R₅ is optionally substituted lower al-kyl or optionally substituted phenyl; and n is 1. In yet another embodiment the compound of the invention has the following substituents:

Ri is CN;

R is optionally substituted benzyl;

2-thienyl, or optionally substituted 1-piperidinyl; 1* is hydrogen, or methyl;

Z is CO, or S0₂ ; and n is 1. h yet another embodiment the compound of the invention has the following substituents:

R_x is CN; R is benzyl; ^"' - - " * -^{" " r}

R₃ is n-propyl, n-butyl, 3-methoxypropyl, 2-thienyl, 5-bromo-2-thienyl, phenyl,^' 4- methoxyphenyl, or 1-piperidiήyl; X -^'" ^■ - - - .. ^■ .- -. . - y

?R-ι is hydrogen;

Z is S0₂ ; and * • n is i.

In yet another embodiment the compound of the invention is selected from the group consisting of:

(R)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-lH- l,4-benzodiazepine-7-carbonitrile;

(R)-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxobutyl)-3-(phenylmethyl)-

IH- 1 ,4-benzodiazepine;

(R)-4-[(5-bromo-2-thienyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl methyl)-3-

(phenyl methyl)-lH-l,4-benzodiazepine; (R)-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl methyl)-4-[(4-methoxyphenyl)sulfonyl]-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyl methyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- IH- 1 ,4-benzodiazepine; (^)-4-(butylsulfonyl)-7-cyano-2,3,4,5-tefrahyά^o-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine;

(R)-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(l- piperidinylsulfonyl)-lH-l,4-benzodiazepine;

( )-4-(3-memoxypropylsulfonyl)-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phehylmethyl)-lH-l,4-benzodiazepine; and pharmaceutically acceptable salts thereof. i certain embodiments of the invention the pharmaceutically acceptable salt is selected from the group consisting of the hydrochloride salt, the methanesulfonic acid salt and the trifluoroacetic acid salt. la one embodiment of the invention compound of the invention is (R)-2,3,4,5-tetrahydro- l-(lH-i-tmdazol-4-ybnethyl)-3-(phenylm^ carbonitrile. . . -* .

In another embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising,, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula: - - - - -- ■ ? -^"- .-^{" "}.^'- - -

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein 1, m, r, s and t are 0 or 1; n is 0, 1 or 2; Y 5 is s lected from the group consisting of CHR¹², S0₂, S0₃, CO, CO₂, O, ?NR¹³, S0₂ ?NR¹⁴, CO?NR¹⁵, C(NCN), C(NCN)NR¹⁶, NR^I7"cθ, NR¹⁸ S0₂, CO?NR¹⁹ NR²⁰, S0₂ NR²¹ NR²², .S(0)(NR²³), S(NR²⁴)(-N?R²⁵), or without Y; Z is selected from the group consisting of CR¹², S_s SO, S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ ? R¹⁴, CONR¹⁵, ? R²⁶ NR²⁷, ONR²⁸, NR²⁹ O, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR.³³ C(NCN), NR³⁴ C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂, 10 OCONR⁴⁰, S(0)(NR⁴¹), S(NR⁴²)(NR⁴³) or CHR.¹² ; or without Z; R⁷, R⁸ are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R⁴⁴; U is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂, NR⁴⁶ C0_2s, NR⁴⁷ CONR⁴⁸, NR⁴⁹ S0₂, NR⁵⁰ S0₂ NR⁵¹, S0₂ NR⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; R⁹, R¹⁰, R¹², R¹³, R¹⁴, l5 p l6 p l7 p l8 p l9 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p30 p31 p32 p33 p34 p35 is. , is. , is. , is. , is. , is. , is. , is. , ts. , is. , is. , ts. , is. , is. , is. , is. , is. , is. , is. , is. , is. ,

- 1i 0~ τ is?.³⁶ , τ is?.³⁷ , x is?.³⁸ , P is.³⁹ , τ is?.⁴⁰ , P is.⁴¹ , x i?s.⁴² , is.⁴³ , xJ?V⁴⁵ , x1?s.⁴⁶ , is.⁴⁷ , P is.⁴⁸ , P is.⁴⁹ , i is?.⁵⁰ , is.⁵¹ , P is.⁵² , x is?.⁵³ , is.⁵⁴ , T is?.⁵⁵ , τ i?s.⁵⁶ , x is?.⁵⁷ ,

R⁵⁸ and R⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl or substituted hetercyclo; R^u and R⁴⁴ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aral-kyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo; R¹, R²,

20 R³, R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl (e.g. CO?NH₂), substituted carbamyl (where nitrogen may be substituted by groups selected from hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo),

25 alkoxycarbonyl; any two of R¹, R², R³, R⁴, R⁵ and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)_P Q wherein Q is NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; and p is 0, 1 or 2; A, B and C are carbon, oxygen, sulfur or nitrogen; D is carbon, oxygen, sulfur or nitrogen or without D; and with the provisos:

1. When 1 and m are both 0, n is not 0;

2. R¹¹ may be hydrogen except when Z is SO, or when Z is O, NR¹³ or S and the carbon to which it is attached is part of a double bond or when Y is S0₂, C0₂, NR¹⁸ S0₂, S(0)(NR²³), or S(NR²⁴)(NR²⁵); .

3. R⁴⁴ may be hydrogen except when U is SO, S0₂, NR⁴⁶ C0₂ or NR⁴⁹ S0₂.

In one embodiment the compound has the formula:

wherein r, s and t are O or 1; l is 0; m is l; n is 1;

Y is selected from the group consisting of CHR¹², S0₂, S0₃, C0₂, O, NR¹³, S0₂ NR¹⁴,

CONR¹⁵, C(NCN), C(NCN)NR¹⁶, NR¹⁷ CO, NR¹⁸ S0₂, CONR¹⁹ NR²⁰, S0₂ NR²¹ NR²²,

S(0)(NR²³), S(NR²⁴)(NR²⁵), or without Y;

Z is selected from the group consisting of S, SO, S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ NR¹⁴,

CONR¹⁵, NR²⁶ NR²⁷, ONR²⁸, NR²⁹ O, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³³ C(NCN), NR³⁴

C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂, OCONR⁴⁰, S(0)(NR⁴¹), or

R , R are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R⁴⁴ ; U is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, NR⁴⁹ S0₂, NR⁵⁰ S0₂ NR⁵¹, S0₂ NR⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹,

R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹, R⁴⁰, R⁴¹, R⁴², R⁴³, R⁴⁵, R⁴⁶, R⁴⁷, R⁴⁸, R⁴⁹, R⁵⁰, R⁵¹, R⁵², R⁵³, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸ and R⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl; R¹¹ and R⁴⁴ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;

R¹, R², R³ R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, substituted carbamyl wherein substituents on the nitrogen- of the substituted carbamyl are selected hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R.,-R , R , R , R. ^• and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH₂, and CH(CH₂)_P Q wherein Q is

NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; wherein p is 0, 1 or 2; and

A, B, C and D are carbon; its enantiόmers, diastereomers, pharmaceutically acceptable salts and solvates thereof; with the provisos that:

1. R¹¹ may be hydrogen except when Z is SO, or when Z is O, NR¹³ or S and the carbon to wliich it is attached is part of a double bond or when Y is S0₂, C0₂, NR S0₂, S(0)(NR²³)₃ or S(NR²⁴)(NR²⁵); and

2. R⁴⁴ may be hydrogen except when U is SO, S0_2; NR⁴⁶ C0₂ or NR⁴⁹ S0₂.

In another embodiment the compound has the following substituents: 1, m, r, s and t are 0 or 1; n is 1 or 2;

Y is CHR¹², S0₂, S0₃, C0₂, S0₂ NR¹⁴, CONR¹⁵ or without Y;

Z is S0₂, S0₃, CO, C0₂, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ CONR³⁸, or NR³⁹ C0₂. In another ambodiment the compound has the following substituents: 1, r, s, and t is 0;

Y is CHR¹², S0₂, S0 NR¹⁴, or CONR¹⁵ or without Y; and Z is S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ or

CONR³⁸, NR³⁹ C0₂.

In yet another embodiment the compound has the following substituents: R⁷, R⁸ is halogen, nitro, cyano or U-R⁴⁴ wherein U is S, O, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, R⁴⁴ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R⁴⁶ and R⁴⁷ is hydrogen, lower alkyl, aryl substituted alkyl or aryl.

In yet another embodiment the the salt is of an organic or inorganic acid.

In yet another embodiment the salt is of hydrogen chloride, hydrogen bromide, methanesulfonic sicid, hydroxyethanesulfomc acid, sulfiiric acid, acetic acid;, trifluoroacetic acid, maleic acid, benzenesulfonic acid, toluenesulfonic acid, nitric acid,-phosphόrk acid, boric acid, tartaric acid, citric acid, succinic acid, benzoic acid, ascorbic acid or salicyclic acid.

- . In yet another embodiment the compound is:

N- [6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-3 -quinolinyl] - 1 - naphthalenesulfonamide, dihydrochloride;

N- [6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-3 -quinolinyl] - 1 - naphthalenecarboxamide, dihydrochloride; N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)methanesulfonamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-irm^azol-4-ylmethyl)-3-quinolinyl]benzenesulfonamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)acetamide, dihydrochloride;

N- [6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-3 -quinolinyl] -N-(4- methoxyphenyl)methyl]methanesulfonamide, monohydrochloride;

N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4- methylphenyl)methyl]methanesulfonamide monohydrochloride; N-[6-cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinohnyl]-N-[(3- methylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl]benzenesulfonamide monohydrochloride; 5 N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahyάro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- ethoxyphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N- 0 (phenylmethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3- dimethoxyphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-qxunolinyl]-N-[(3,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride; 5 N-[6-Cyano-l,2,3,4-tetrahyά^o-l-(lH-imidazol-4-ylmethyl)-3-quinbli^"nyl]-N-[(-l- naphthalenyl)methyl]benzenesulfonamide monohydrochloride; - " - ^~ N-[6-Cyario-l,2,-3,4-teteahydrό-l-(lH-im^ - . - thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Gymo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl).-3-quinolinyl]-N-[(2,5- 0 dimethylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- chlorophenyl)methyl]benzenesulfonamide monohydrochloride; 5 N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- fluorophenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-i-midazol-4-ylmethyl)-3-quinolinyl]-N-[(3- pyridyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-ύnidazol-5-yl]memyl]-3-quinolinyl]-N- 30 (phenylmethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3- thiophenemethyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)methanesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmemyl)methanesulfonamide monohydrochloride;

(R)-N-[6-Cyano-l,2,3,4-tefrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride.

In yet another embodiment, the invention is a method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

10 or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein Y is selected from the group consisting of CHR¹², S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ NR¹⁴, CONR¹⁵, C(NCN), C(NCN)NR¹⁶, NR¹⁷ CO, NR¹⁸ S0₂, CONR¹⁹ NR²⁰, S0₂ NR²¹ NR²², S(0)(NR²³), and S(NR²⁴)(NR²⁵), or without Y; Z is selected from the group consisting of S, SO, S0₂, S0₃, CO, C0₂, O, ?NR¹³, S0₂ ?NR¹⁴, CONR¹⁵,

15 NR²⁶ NR²⁷, ONR²⁸, NR²⁹ O, NR³⁰ S0₂ NR³¹, NR³² S0₂, ?NR³³ C(NCN), NR³⁴ C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C02, OCONR⁴⁰, S(0)(NR⁴¹), and S(NR⁴²)(NR⁴³); R⁷ and R⁸ are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R⁴⁴; U is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, NR⁴⁹ S0₂, ?NR⁵⁰ S0₂ NR⁵¹, S0₂ ? R⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; R⁹, R¹⁰,

O λC\)\ I is?.¹² , T is?.¹³ , i Ps.¹⁴ , P is.¹⁵ , P is.¹⁶ , P is.¹⁷ , P is.¹⁸ , P i .¹⁹ , P is.²⁰ , P is.²¹ , P is.²² , P is.²³ , P is.²⁴ , P is.²⁵ , P is.²⁶ , P is.²⁷ , P is.²⁸ , P is.²⁹ , P is.³⁰ , P is.³¹ , P is.³² , p33 -_p34 35 p36 p37 p38 p39 p40 p41 p42 p43 _p44 _p45 p46 _p47 _p48 p49 _p50 _p51 _p52 _{p 5}3 is. , ts , is. , is. , -K. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. ,

R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, andR⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl and aryl; R¹¹ and R⁴⁴ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, 25 aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; R¹, R², R³, R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, and substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, aralkyl, substituted aryl, heterocyclo, and substituted heterocyclo; any two of R¹, R², R³, R⁴, R⁵ and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH₂ and CH(CH₂)_P Q wherein Q is NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomer, diastereomer, pharmaceutically acceptable salt or solvate thereof; with the provisos that:

1. R¹¹ may be hydrogen except when Z is SO, or when Z is O, ?NR¹³ or S and the carbon to which it is attached is part of a double bond or when Y is S0₂, C0₂, NR¹⁸ S0₂, S(0)( R²³), or S(NR²⁴)(NR²⁵); and ' 2. ^ may be hydrogen except when If is SO, S0₂, NR⁴⁶ C0₂ or NR⁴⁹ S0₂7

28. The method of claim 27 wherein r, s and t are 0 or 1 ; ^''^"■" is CHR¹²; S0₂, S0₃, C0 C0₂,S0₂ NR¹⁴, CONR¹⁵ of without Ϋ; ^•" - " - ^" Z is CR¹², S0₂, S0₃, CO, C0₂, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z. n one embodiment of this aspect of the invention r, s and t are 0 or 1; Y is CHR¹², S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵ or without Y;

Z is CR¹², S0₂, S0₃, CO, C0₂, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, ?NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z. In yet another embodiment r, s, and t is 0; Y is CHR¹², S0₂, CO, S0₂ ?NR¹⁴, or CONR¹⁵ or without Y; and Z is CR¹², S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, ?NR³⁶ CO, ?NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z.

In yet another embodiments R⁷, R⁸ is halogen, nitro, cyano or U--R⁴⁴ wherein U is S, O, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, R⁴⁴ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R⁴⁶ and R⁴⁷ is hydrogen, lower alkyl, aryl substituted alkyl or aryl.

In one embodiment the compound of the invention is selected from the group consisting of: N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-l- naphthalenesulfonamide, dihydrochloride; N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-mιidazol-4-ylmethyl)-3-quinolinyl]-l- naphthalenecarboxamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)methanesulfonamide, dihydrochloride; N-[6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-3 -quinolinyl]benzenesulfonamide, dihydrochloride;

N-[6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-3 -quinolinyl] -N-

(phenylmethyl)acetamide, dihydrochloride;

N-[6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -quinolinyl] -N-(4- methoxyphenyl)methyl]methanesulfonamide, monohydrochloride;

N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4- methylphenyl)methyl]methanesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinohnyl]-N-[(3- methylρhenyl)methyl]benzenesulfonamide monohydrochloride; ' N-[6-cyano-l,2,3,4 tefrahydro-l-(lH-rmidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl]benzenesulfonamide monohydrochloride; "'- N-[6-cyano-l,2;3,4 etrahydro-l-(lH-irmdazol-4-ylniethyl)-3-quinolinyl]-N- ^• - "

(phenylethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- ethoxyphenyl)methyl]benzenesulfonamide monohydrochloride; -

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahy(ho-l-(lH-imidazol-4-ylme l)-3-qύinolinyl]-N-[(2,3- dimethoxyphenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahyά^o-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(l- naphthalenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- thiophene)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- chlorophenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- fluorophenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- pyridyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]memyl]-3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahyα^o-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3-0 thiophenemethyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenylmethyl)methanesulfonamide monohydrochloride;

N-[6-Cyano- 1 ,2,3,4-tetrahydro-l -[[ 1 -(methyl)- lH-imidazol-5-yl]methyl]-3-quinohnyl]-N- (phenylmethyl)methanesulfonamide monohydrochloride; 5 ( )-N-[6-Cyano-l,2,3,4-tefrahydro-l-[[α-(methyl)-lHri idazol-5-yl]methyl]^3-quinolinyl]-N- (phenylmethyl)benzenesulfonamide monohydrochloride.

-hi_. another embodiment, the invention-is a. method of treating a synucleinopathic subject,-^" the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formμla: Q

^' or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a thera eutically effective amount. In one aspect of the invention the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder. In a preferred embodiment the subject is a human. In certain embodiments of the invention the effective amount of the compound of the invention 5 comprises about 10 ng/kg of body weight to about 1000 mg/kg of body weight at a frequency of administration from once a day to once a month. In one embodiment the invention comprises further administering to the subject an amount of one or more non-farnesyl transferase inhibitor compounds effective to treat a neurological disorder. In one embodiment of the invention each non-farnesyl transferase inhibitor compound is selected from the group consisting of: dopamine

10 agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and ?NMDA antagonist, hi one embodiment of the invention each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.

Another aspect of the invention provides an article of manufacture comprising packaging

15. , material and a farnesyl transferase inhibitor compound,-wherein the article of manufacture ^""^" .. . further comprises a label or package insert indicating that the farnesyl transferase inhibitor cpmpound-can be administered to a subject for-treating a synucleinopathy. In -a preferred - embodiment the subject is a human, hi one embodiment the invention comprises further administering to the subject an amount of one or more non-farnesyl transferase inhibitor

20 compounds effective to treat a neurological disorder. In one embodiment of the invention each non-famesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and ?NMDA antagonist, h one embodiment of the invention each non-farnesyl trasferase inhibitor compound is selected from

25 the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors. hi methods of the invention, the term "synucleinopathic subject" refers to a subject that is affected by or at risk of developing a synucleinopathy (e.g. predisposed, for example genetically predisposed, to developing a synucleinopathy) and/or any neurodegenerative disorders characterized by pathological synuclein aggregations. Several neurodegenerative

30 disorders including Parkinson's Disease, Diffuse Lewy Body disease (DLBD) and Multiple System Atrophy (MSA) are collectively grouped as synucleinopathies.

Synucleins are small proteins (123 to 143 amino acids) characterized by repetitive imperfect repeats SEQ ID NO: 8 (KT-KEGV) distributed throughout most of the amino terminal half of the polypeptide in the acidic carboxy-terminal region. There are three human synuclein

35 proteins termed , β, and γ, and they are encoded by separate genes mapped to chromosomes 4221.3-q22, 5q23 and 10q23.2-q23.3, respectively. The most recently cloned synuclein protein synoretin, has a close homology to γ-synuclein and is predominantly expressed within the retina, α-synuclein, also referred to as non-amyloid component of senile plaques precursor protein (NACP), SYN1 or synelfm, is a heat-stable, "natively unfolded" protein of poorly defined function. It is predominantly expressed in the central nervous system (GNS) neurons where it is localized to presynaptic terminals. Electron microscopy studies have localized α-synuclein in close proximity to synaptic vesicles at axonal termini, suggesting a role for α-synuclein in neurotransmission or synaptic organization, and biochemical analysis has revealed that a small fraction of α-synuclein may be associated with vesicular membranes but most α-synuclein is cytosolic.

Genetic and histopathological evidence supports the idea that α-synuclein is the major component of several proteinaceous inclusions characteristic of specific neurodegenerative diseases. Pathological synuclein aggregations are restricted to the α-synuclein isoforms, as β and γ synucleins have not been detected in these inclusions. The presence of α-synuclein positive aggregates is disease specific. Lewy bodies; neuronal fibrous cytoplasmic inclusions that are histopathological hallmarks of Par-kinson's Disease (PD) and Diffuse Lewy Body disease (DLBD) are strongly labeled with- antibodies to α-synuclein? Dystroρhic--ubiquitiri- positive neurites associated with PD pathology, termed Lewy neurites (LN) and CA2/CA3 ubiquitin neurites are also α-synuclein positive. Furthermore, pale bodies, putative precursors of - LBs, thread-like structures in the perikarya of slightly swollen neurons and glial silver positive inclusions in the midbrains of patients with LB diseases are also immunoreactive for α- synuclein. _ α-synuclein is likely the major component of glial cell inclusions (GCIs) and . neuronal cytoplasmic inclusions in MSA and Hallervorden-Spatz disease (brain iron accumulation type 1). α-synuclein immunoreactivity is present in some dystrophic neurites in senile plaques in Alzheimer's Disease, but is not detected in Pick bodies neurofibrillary tangles (NFTs), neurophil threads, or in neuronal or glial inclusion characteristic of Progressive Supranuclear Palsy, Corticolbasal Degeneration, motor neuron disease and trinucleotide-repeat diseases.

Further evidence supports the notion that α-synuclein is the actual building block of the fibrillary components of LBs, LNs and GCIs. -hnmunoelectron microscopic studies have demonstrated that these fibrils are intensely labeled with α-synuclein antibodies in situ. Sarcosyl-insoluble α-synuclein filaments with straight and twisted moφhologies can also be observed in extracts of DLBD and MSA brains. Moreover, α-synuclein can assemble in vitro into elongated homopolymers with similar widths as sarcosyl-insoluble fibrils or filaments visualized in situ. Polymerization is associated with a concomitant change in secondary structure from random coil to anti-parallel /3-sheet structure consistent with the Thioflavine-S reactivity of these filaments. Furthermore, the PD-association with α-synuclein mutation, A53T, may accelerate this process, as recombinant A53T α-synuclein has a greater propensity to polymerize than wild-type α-synuclein. This mutation also affects the ultrastructure of the polymers; the filaments are slightly wider and are more twisted in appearance, as if assembled from two protofilaments. The A30P mutation may also modestly increase the propensity of α- synuclein to polymerize, but the pathological effects of this mutation also maybe related to its reduced binding to vesicles. Interestingly, carboxyl-terminally truncated α-synuclein may be more prone to form filaments than the full-length protein. According to the invention, the proteosomal degradation of α-synuclein is a mediated by parkin and neuronal ubiquitin C-terminal hydrolase (UCH-L1). Parkin is an E3 ligase that ubiquitinylates α-synuclein and thereby tags it for degradation. UCH-L1 acts in normal neuronal tissues to cleave the ubiquitinylated proteins that are products of the proteosomal degradation of the polyubiquitinylated protems. - The invention provides methods for treating synucleinopathic disorders using inhibitors of farnesyl transferase. It has been now discovered that UCH-L1 is famesylated in vivo. UCH-

- LI is associated with -the membrane and this membrane, association is mediated by-famesylation.^'-

Farnesylated UCH-L1 also stabilizes the accumulation of α-synuclein. The invention relates to

. the. prevention or inhibition of UCH-L1 farnesylation which would result in UCH-L1 membrane disassociation and acceleration of the degradation of α-synuclein. Since α-synuclein accumulation is pathogenic in PD, DLBD, and MSA, an increased degradation of α-synuclein and/or inhibition of α-synuclein accumulation ameliorates the toxicity associated with a pathogenic accumulation of α-synuclein. - - .

The modification of a protein by a farnesyl group can have an important effect on function for a number of proteins. Famesylated proteins typically undergo further C-terminal modification events that include a proteolytic removal of three C-terminal amino acids and carboxymethylation of C-terminal cystines. These C-terminal modifications facilitate protein- membrane association as well as protein-protein interactions. Farnesylation is catalyzed by a protein farnesyltransferase (FTase), a heterodimeric enzyme that recognizes the CAAX motif present at the C-terminus of the substrate protein. FTase transfers a farnesyl group from farnesyl pyrophosphate and forms a thioether linkage between the farnesyl and the cystine residues in the CAAX motif. A number of inhibitors of FDase have been developed and are -known in the art. However, the invention provides novel methods for using certain farnesyl transferase inhibitors to treat subjects having symptoms associated with α-synuclein accumulation. In methods of the invention, the term "synucleionopathy" refers to neurological disorders that are characterized by a pathological accumulation of α-synuclein. This group of disorders includes PD, DLBD and MSA.

Parkinson's Disease (PD) is a neurological disorder characterized by brady inesia, shuffling gait, postural instability, tremor, and a loss of automatic movement. It is due to the loss of dopamine-containing substantia nigra cells. It appears that about 50% of the cells need to be lost before symptoms appear. Associated symptoms often include rigidity, difficulty initiating movement (akinesia), small handwriting (micrograp-hia), seborrhea, orthostatic hypertension, urinary difficulties, constipation, lymph pain, depression, dementia (up to a third of the patients), smelling disturbances (occurs early). Orthostatic hypertension might occur associated with the disease or as a complication of medication. Patients with Parkinsonism have greater mortality, about two times compared to general population without PD. This is attributed to greater frailty or reduced mobility. >

The term "synucleinopathic subject" encompasses a. subject that is affected by, or is at risk of developing PD. These subjects can be readily identified by persons of ordinary skill in the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

.. Diagnosis of PD is mainly clinical and is based on. thexlinical findings listed above." - There are many conditions which may be mistaken for Parlrinsonism. Among the most common are side effects of drugs, mainly the major tranquilizers, such as Haldol, strokes involving the basal ganglea, degenerative disorders, such as progressive supranuclear palsy (PSP), - - . olivopontocerebellar degeneration (OPCD), MSA, and Huntington's Disease. The pathological hallmark of PD are Lewy bodies, which are intracytoplasmatic inclusion bodies in effected neurons of the substantion nigra. Recently, α-synuclein has been identified as the main component of Lewy bodies in sporadic Parldnsonism. Although Parkinson's can be clearly traced to genetic factors, viruses, stroke, or toxins in few individuals for the most part the cause of Parkinson's in any particular case is unknown (this is referred to as sporadic PD). Environmental influences include drinking well water, farming and industrial exposure to heavy metals (iron, zinc, copper, mercury, magnesium and manganese), alkylated phosphates and orthonal chlorines. Paraquat (a herbicide) has been associated with increased prevalence of Parkinsonism, cigarette smo-king is associated with the decrease incidence. The current consensus is that Parkinsonism may either be caused by an uncommon toxin combined with high genetic susceptibility or a common toxin combined with relatively low genetic susceptibility.

Subjects that are at risk of developing PD can be identified for example by genetic analysis. There is good evidence for genetic factors associated with PD. Large pedigrees of autosomal dominantly inherited PDs have been reported. A mutation in α-synuclein is responsible for one pedigree.

Methods of the invention can be used in combination with one or more alternative medications, including medications that are currently used to treat synucleinopathies or symptoms arising as side-effects of the disease or of the aforementioned medications.

For example, methods of the invention can be used in combination with medications for treating PD. Levodopa mainly in the form of combination product containing carbodopa and levodopa (Synemat and Synemat CR) is the mainstay of treatment and is the most effective agent for the treatment of PD. Levodopa is a dopamine precursor, a substance that is converted into dopamine by an enzyme in the brain. Carbodopa is a peripheral dicarboxylase inhibitor which prevents side effects and lower the overall dosage requirement. The starting dose of Synemat is 125/100 tablet prior to each meal. User maintenance dose is lower. Dyskinesias may restilt from overdose and also are commonly seen after prolonged (e.g., years) use. Direct acting dopamine agonists may have less of this side effect. Orthostatic hypertension may . respond to-increased carbodopa. About 15% ofpatients do not respond to levodopa. - Dopamine is metabolized to potentially toxic-free radicals and some feel that a direct-acting dopamine -agonist should be used early to.-supplement a dopamine; agonist?. Stalevo (carbodopa, levodopa, and entacapone) is a new combination tablet for patients who experience signs and symptoms of "wearing-off '. The tablet combines carbodopa, levodopa, (the most widely agents for^D) with entacapone, while carbodopa reduces the side effects of levodopa, entacapone extends the time levodopa is active in the brain, up to 10% longer. .

Amantidine (Symmetrel) is a mild agent thought to work by blocking the re-uptake of dopamine into presynaptic neurons. It also activates the release of dopamine from storage sites and has a glutamate receptor blocking activity. It is widely used as early monotherapy and the dosing is 200 to 300 mg daily. Amantidine is particularly helpful in patients with predominant tremor. Side effects include ankle swelling and red blotches. Unfortunately, it's effect in more advanced PD is often short-lived with patients reporting a "fallout effect".

Anticholinergics (trihexyphenidyl, benztropine mesylate, procyclidine, artane, cogentin) do not act directly on the dopaminergic system. Direct-acting dopamine agonists include bromocriptidine (Parlodel), pergolide (Permax), ropinirol (Requip), and pramipexole (Mirapex). These agents cost substantially more than the levodopa (Synemat) with controversial additional benefits. Depending on which dopamine receptor is being stimulated, Dl and D2 agonist can exert anti-Par-kinson effects by stimulating the Dl and D2 receptors, such as Ergolide. Mirapex and Requip are the newer agents. Both are somewhat selected for dopamine receptors with highest affinity for the D2 receptor and also activity at the D3 receptor. Direct dopamine agonists, in general, are more likely to produce adverse neuro psychiatric side effects than levodopa, such as confusion. Unlike levodopa, direct dopamine agonists do not undergo conversion to dopamine and thus do not produce potentially toxic metabolites. It is also possible that the early use of direct dopamine agonist might protect against the development of late 5 complications of dopamine, such as the "on-off effect.

Monoaminoxidase-B inhibitors (MAO) such as selegiline (Diprenyl, or Eldepryl), taken in a low dose, can initially reduce the progression of Parkinsonism. These compounds can be used as an adjunctive medication. A study has documented that selegiline delays the need for levodopa by roughly three months.

10 Catechol-O-methyltransferase inhibitors (COMT) can also be used in combination treatments of the invention. Catechol-O-methyltransferase is an enzyme that degrades levodopa and inhibitors can be used to reduce the rate of degradation. Entocapone is a peripherally acting COMT inhibitor, which can be used in certain, methods and compositions of the invention. Tasmar or Tolcapone, approved by the FDA in 1997, can also be used in certain methods and ~1.5 compositions of the invention. Psychiatric adverse effects that are induced by PD medication include psychosis, confusion, agitation, hallucinations, and delusions. These can be treated by

^~ decreasing -dopamine medication, reducing or discontinuing anlicholffiergic.s, amantidine or selegiline or by using clozipine, for example at doses of 6.25 to 50 mg/day.

Methods of the invention can also be used in combination with surgical therapies for the

20 treatment of PD. Surgical treatment is presently recommended for those who have failed medical management of PD. Unilateral Thallamotomy - can be used to reduce tremor. It is considered for patients with unilateral, tremor not responding to medication. The improvement fades with time. Bilateral procedures are not advised. Unilateral pallidotomy is an effective tec-hnique for reducing contralateral levodopamine dyskinesias. Unilateral deep brain

25 stimulation of the thalamus for tremor may also be a benefit for tremor. Neurotransplantation is no longer felt to be an effective treatment. Gamma knife surgery - thalamotomy or pallidotomy - can be performed to focus radiation. In addition to surgery and medication, physical therapy in Parkinsonism maintains muscle tone, flexibility, and improves posture and gait.

According to the invention, the term "synucleinopathic subject" also encompasses a

30 subject that is affected by, or is at risk of developing DLBD. These subjects can be readily identified by persons of ordinary s-kill in the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

DLBD is the second commonest cause of neurodegenerative dementia in older people, it effects 7% of the general population older than 65 years and 30% of those aged over 80 years. It

35 is part of arange of clinical presentations that share a neurotic pathology base ofnormal aggregation of the synaptic protein α-synuclein. DLBD has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's Disease. An "one year rule" can been used to separate DLBD from PD. According to this rule, onset of dementia within 12 months of Parkinsonism qualifies as DLBD, whereas more than 12 months of Parkinsonism before onset of dementia qualifies as PD. The central features of DLBD include progressive cognitive decline of sufficient magnitude to interfere with normal social and occupational function. Prominent or persistent memory impairment does not necessarily occur in the early stages, but it is evident with progression in most cases. Deficits on tests of attention and of frontal cortical skills and visual spatial ability can be especially prominent.

Core diagnostic features, two of which are essential for diagnosis of probable and one for possible DLBD are fluctuating cognition with pronounced variations in attention and alertness, recurrent visual hallucinations that are typically well-formed and detailed, and spontaneous features of Parlrinsonism. n addition, there can be some supportive features, such as repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, hallucinations and other modalities, ?REM sleep behavior disorder- and depression. Patients with DLBD do better than those with Alzheimer's Diseasein tests of verbal memory," but worse on visual performance tests. This profile can be maintained across the range of severity of the disease, but can be harder to recognize in the later stages owing to global difficulties. DLBD typically presents with recurring episodes of confusion on a background of progressive deterioration. Patients with DLBD show a combination of cortical and subcortical neuropsychological impairments with substantial attention deficits and prominent frontal subcortical and visual special dysftmction. These help differentiate this disorder from Alzheimer's Disease. Rapid eye movement (REM), sleep behavior and disorder is a parasomnia manifested by vivid and frightening dreams associated with simple or complex motor behavior during REM sleep. This disorder is frequently associated with the synucleinopathies, DLBD, PD and MSA, but it rarely occurs in amyloidopat-hies and taupathies. The neuropsychological pattern of impairment in REM sleep behavior disorder/dementia is similar to that reported in DLBD and qualitatively different from that reported in Alzheimer's Disease. Neuropathological studies of REM sleep behavior disorder associated with neurodegenerative disorder have shown Lewy body disease or multiple system atrophy. REM sleep wakefulness disassociations (REM sleep behavior disorder, daytime hypersomnolence, hallucinations, cataplexy) characteristic of narcolepsy can explain several feature of DLBD, as well as PD. Sleep disorders could not contribute to the fluctuations typical of DLBD and their treatment can improve fluctuations and quality of life. Subjects at risk of developing DLBD can be identified. Repeated falls, syncope, transient loss of consciousness, and depression are common in older people with cognitive impairment and can serve as (a red flag) to a possible diagnosis of DLBD. By contrast, narcoleptic sensitivity in REM sleep behavior disorder can be highly predictive of DLBD. Their 5 detection depends on the clinicians having a high index of suspicion and asking appropriate screening questions.

Clinical diagnosis of synucleinopathic subjects that are affected by or at risk of developing LBD can be supported by neuroimaging investigations. Changes associated with DLBD include preservation of hippocampal, and medialtemperalobe volume on -M-RI and sipital

10 hypeφrofusion on SPECT. Other features, such as generalized atrophy, white medichanges and rates of progression of whole brain atrophy are not helpful in differential diagnosis. Dopamine transported a loss in the caudate and putamen, a marker of nigrostriatal degeneration can be detected by dopomenergic SPECT and can prove helpful in clinical differential diagnosis. A sensitivity of 83% and specificity of 100% has been reported for an abnormal scan with an

15 autopsy.diagnosis of DLBD. ^••-••«. -^~- ^~-^~ ~ ^■- ^■ . -^■

- Consensus criteria for diagnosing DLBD include ubiquitin immunohistochemistry for

- - - -Lewy body identification and staging into three categories; brain .stem predominant, limbic, or. - r neocortical, depending on the numbers and distribution of Lewy bodies. The recently-developed α-synuclein immunohistochemistry is a better marker that visualizes more Lewy bodies and. also 0 better source previously under recognized neurotic pathology, termed Lewy neurites. Use of antibodies to α-synuclein moves the diagnostic rating for many DLBD cases from brain stem and limbic groups into the neocortical group.

In most patients with DLBD, there are no genetic mutations in the α-synuclein or other Parkinson's Disease genes. Pathological up-regulation of normal, wild-type α-synuclein due to

25 increased mRNA expression is a possible mechanism, or Lewy bodies may form because α- synuclein becomes insoluble or more able to aggregate for some reason. Another possibility is that α-synuclein is abnormally processed, for example, by dysfunctional proteosome system and ' that toxic "proto fibrils" are therefore produced. Sequestering of these toxic fibrils into Lewy bodies could reflect an effort by the neurons to combat biological stress inside the cell, rather

30 than their simply being neurodegenerative debris.

Target symptoms for the accurate of DLBD can include extrapyramidal motor features, cognitive impairment, neuropsychiatric features (including hallucinations, depression, sleep disorder, and associated behavioral disturbances) or autonomic dysfunction.

Methods of the invention can be used in combination with one or more alternative

35 medications for treating DLBD. For example, lowest acceptable doses of levodopa can be used for treating DLBD. D2-receptor antagonists, particularly traditional neuroleptic agents can provoke severe sensitivity reactions in DLBD subjects with an increase in mortality of two to three times. Cholinsterase inhibitors dicussed above are also used in the treatment of DLBD. According to the invention, the term "synucleinopathic subject" also encompasses a subject that is affected by, or is at risk of developing MSA. These subjects can be readily identified by persons of ordinary skill in the art by symptomatic diagnosis or by genetic screening, brain scans, SPEC, PET imaging etc.

MSA is a neurodegenerative disease marked by a combination of symptoms; affecting movement, blood pressure, and other body functions, hence the label "multiple system atrophy". The cause of MSA is unknown. Symptoms of MSA vary in distribution of onset and severity from person to person. Because of this, three different diseases were initially described to accomplish this range of symptoms; Shy-Drager syndrome, striatonigral degeneration (SD), and olivopontocerebellar atrophy (OPCA). - :,

In Shy-Drager syndrome, the most prominent symptoms are those involving the autonomic-system; blood pressure, urinary function, and other functious not involving conscious control. -Striatonigral degeneration, causes Parkinsonism symptoms,- such as slowed movements and.rigidity, while OP-.CA principally effects balance, coordination and speech. The symptoms for MSA can also include orthostatic hypertension, male impotence, urinary difficulties, constipation, speech and swallowing difficulties, and blurred vision. • The initial diagnosis of MSA is usually made by carefully interyiewing.the patient, and performing a physical examination. Several types of brain imaging, including computer histomography, scans, magnetic resonance imaging (MRT), and positron emission tomography (PET), are used. Pharmacological challenge tests (administering certain drugs in the presence of various types of movement of the patient) may also be of help in those patients with typical Parlrinsonism signs. An incomplete and relatively poor response to dopamine replacement therapy, such as Sinemet, may be a clue that MSA is present. A characteristic involvement of multiple brain systems is a defining feature of MSA and one that an autopsy confirms the diagnosis. Patients with MSA can have the presence of glial cytoplasmic inclusions in certain types of brain cells, as well. Lewy bodies are not present in MSA. In comparison to Parkinson's, in addition to the poor response to Sinemet, there are a few other observations that are suggested for MSA, such as low blood pressure on standing, difficulty with urination, use of a wheelchair, loud snoring or loud breathing, and frequent nighttime urination.

Methods of the invention can be used in combination with one or more alternative medications for treating MSA. Typically, the drugs that can be used to treat various symptoms of MSA become less effective as the disease progresses. Levodopa and dopamine agonists used to treat PD are sometimes effective for the slowness and rigidity of MSA. Orthostatic hypertension can be improved with cortisone, midodrine, or other drugs that raise blood pressure. Male impotence may be treated with penile implants or drags. Incontinence may be treated with medication or catheterization. Constipation may improve with increased dietary fiber or laxatives.

According to the invention, the term "treatment" includes prophylaxis and therapy, and includes managing a synucleinopathic subject's symptoms and halting the progression of the synucleinopathy. Treatment includes preventing, slowing, stopping, or reversing (e.g. curing) the development of a synucleinopathy, and/or the onset of certain symptoms associated with a synucleinopathy in a subj ect with, or at risk of developing, a synucleinopathy or a related disorder. Therapy includes preventing, slowing, stopping, or reversing (e.g. curing) the accumulation of α-synuclein in a subject with a synucleinopathy. Therapy also includes decreasing the. amount of accumulated α-synuclein in a subject with a synucleinopathy.

The phrase "therapeutically-effective amount" as used herein means that amount of a compound, material, or composition comprising a compound of the present invention whichis effective for producing some desired therapeutic effectin a subject at a reasonable benefit risk -ratio-applicableio any medical freatment. Accordingly, a therapeutically effective amount. - prevents, minimizes, or reverses disease progression associated with a synucleinopathy. Disease progression can be monitored by clinical observations, laboratory and-neuroimaging -. . investigations apparent to a person skilled in the art. A therapeutically effective amount can be an amount that is effective in a single dose or an amount that is effective as part of a multi-dose therapy, for example an amount that is administered in two or more doses or an amount that is administered chronically.

The "pharmaceutically acceptable acid or base addition salts" mentioned herein are meant to comprise the therapeutically active non-toxic acid and non-toxic base addition salt forms that the compounds are able to form. The compounds that have basic properties can be converted into their pharmaceutically acceptable acid addition salts by treating the base form with an appropriate acid. Appropriate acids include, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfiiric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic (i.e. butanedioic acid), maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclamic, salicylic, p- aminosalicylic, pamoic and the like acids.

The compounds that have acidic properties can be converted into their pharmaceutically acceptable base addition salts by treating the acid form with a suitable organic or inorganic base. Appropriate base salt forms include, for example, the ammonium salts, the alkali and earth alkaline metal salts, e.g. the lithium, sodium, potassium, magnesium, calcium salts and the like, salts with organic bases, e.g. the benzathine, N-methyl-D-glucamine, hydrabamine salts, and salts with amino acids such as, for example, arginine, lysine and the like. 5 The terms acid or base addition salt also comprise the hydrates and the solvent addition forms which the compounds are able to form. Examples of such forms are e.g. hydrates, alcoholates and the like.

The term stereochemically isomeric forms of compounds, as used herein, include all possible compounds made up of the same atoms bonded by the same sequence of bonds but

10 having different three-dimensional structures wMch are not interchangeable, which the compounds may possess. Unless otherwise mentioned or indicated, the chemical designation of a compound encompasses the mixture of all possible stereochemically isomeric forms that the compound can take. The mixture can contain all.diastereomers and/or enantiomers of the basic molecular structure of the compound. All stereochemically isomeric forms of the compounds - 15- both in pure form or in admixture with each otheπate intended to be embraced within the scope of the present invention.- .-• - - -• - — -- --. -. -. ' Some.- of the compounds may alsoΛxist in -their tautomeric-forms Such forms although not explicitly mdicated in the above formula are intended to be included within the scope of the present invention.

20 . The methods and structures described herein relating to compounds and compositions of the invention also apply to the pharmaceutically acceptable acid or base addition salts and all stereoisomeric forms of these compounds and compositions. . fri the compounds and compositions of the invention, the term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl

25 groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In preferred embodiments, a straight chain or branched chain alkyl has 12 or fewer carbon atoms in its backbone (e.g., C₁-C₁₂ for straight chain, C₃-Cι₂ for branched chain), and more preferably 6 or fewer, and even more preferably 4 or fewer. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably

30 have 5, 6 or 7 carbons in the ring structure.

Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure, and even more preferably from one to four carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. Preferred alkyl groups are lower alkyls. In preferred embodiments, a substituent designated herein as al-kyl is a lower alkyl.

As used herein, the term "halogen" designates -F, -Cl, -Br or -I; the term "sulfhydryl" means -SH; and the term "hydroxyl" means -OH. The term "methyl" refers to the monovalent radical -CH₃, and the term "methoxyl" refers to the monovalent radical -CH₂OH.

The term "aral-kyl" or "arylalkyl", as used herein, refers to an alkyl group substituted with an aryl group (e.g., an aromatic or heteroaromatic group).

The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

The term "aryl" as used herein includes 5-, 6- and 7-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like Those-aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles" or "heteroaromatics." The aromatic ring can be substituted at oni or more ring positions -witlrsuch substituents as described above; for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, -CF₃, - CN, or the like. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are "fused rings") wherein at least one of the rings is aromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls. The terms "ortho", "meta" and "para" apply to 1,2-, 1,3- and 1,4-disubstituted benzenes, respectively. For example, the names 1,2-dimethylbenzene and ortho-dimethylbenzene are synonymous.

The terms "heterocyclyl" or "heterocyclic group" or "heteroaryl" refer to 3- to 10- membered ring structures, more preferably 3- to 7-membered rings, whose ring structures include one to four heteroatoms. Heterocycles can also be polycycles. Heterocyclyl groups include, for example, thiophene, benzothiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxathiin, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, fiirazan, phenoxazine, pyrrolidine, oxolane, t-hiolane, oxazole, piperidine, piperazine, moφholine, lactones, lactams such as azetidinones and pyrrolidinones, sultams, sultones, and the like. The heterocyclic ring can be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, -CF₃, -CN, or the like.

As used herein, the definition of each expression, e.g. alkyl, m, n, etc., when it occurs more than orice in any structure, is intended to be independent of its definition elsewhere in the same structure.

It will be understood that "substitution" or "substituted with" includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term "substituted" is. contemplated to include all permissible substituentS'of-organic compounds. In a broad aspect, the permissible-substituents include - acyclic and cyclic^branchedrand unbranched, carhocyclic and-heterocycϊie, ^'aromatic and- .- -^:. .. nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described herein above. The permissible substituents can be one or more and the same₍ or- ... different for appropriate organic compounds. For puφo.ses of this invention, the heteroatoms - ., such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms; This invention, is, not intended to be limited in any manner by the permissible substituents of organic compounds. Certain compounds of the present invention may exist in particular geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and trαw-s-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention. Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group. All such isomers, as well as mixtures thereof, are intended to be included in this invention, hi certain embodiments, the present invention relates to a compound represented by any of the structures outlined herein, wherein the compound is a single stereoisomer.

If, for instance, a particular enantiomer of a compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatograpliic means well known in the art, and subsequent recovery of the pure enantiomers. Contemplated equivalents of the compounds described above include compounds which otherwise correspond thereto, and which have the same general properties thereof (e.g., functioning as anti-synucleinopathy farnesyl transferase inhibitor compounds), wherein one or more simple variations of substituents are made which do not adversely affect the efficacy of the compound. In general, the compounds of the present invention may be prepared by the methods illustrated in the general reaction schemes as, for example, described below, or by modifications thereof, using readily available starting materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variants, which are in themselves known, but are not mentioned here.

For puφoses of this invention, the chemical elements are identified in accordance with the Periodic Tablg of the Elements, CAS version, Handbook-of Chemistry and Physics,.67th. Ed., 1986-87, inside cover. -----

_-7jn another aspect, the present invention provides "pharmaceutically acceptable" . . --. compositions, which comprise a therapeutically effective amount of one or more of the . compounds described herein, formulated together with one or more pharmaceutically acceptable carriers (additives) and/or diluents. As.described in detail, -the -pharmaceutical compositions of . the present invention may be specially formulated for administration in solid or liquid form, including those adapted for the following: oral administration, for example, drenches (aqueous or non-aqueous solutions or suspensions), tablets, e.g., those targeted for buccal, sublingual, and systemic absoφtion, boluses, powders; granules, pastes for application to the tongue; parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; topical application, for example, as a cream, ointment, or a controUed-release patch or spray applied to the skin, lungs, or oral cavity; intravaginally or intrarectally, for example, as a pessary, cream or foam; sublingually; ocularly; transdermally; or nasally, pulmonary and to other mucosal surfaces.

The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio . The phrase "pharmaceutically-acceptable carrier" as used herein means a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically-acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as com starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; pH buffered solutions; polyesters, polycarbonates.-and/or polyanhydrides; and other -r- - -- non-toxic compatible substances-employed in pharmaceutical formulations. ^"- ". "-: -- As set outrhereiή, certain embodiments of the present compounds^nay contain a basic functional group, such as amino oralkylamino, and are, thus, capable of forming pharmaceutically-acceptable salts with pharmaceutically-acceptable acids. The term "pharmaceutically-acceptable salts" in this respect refers to the relatively- non-toxic, inorganic and organic acid addition salts of compounds of the present invention. These salts can be prepared in situ in the administration vehicle or the dosage form manufacturing process, or by separately reacting a purified compound of the invention in its free base form with a suitable organic or inorganic acid, and isolating the salt thus formed during subsequent purification. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like. (See, for example, Berge et al. (1977) "Pharmaceutical Salts", J. Pharm. Sci. 66:1-19) The pharmaceutically acceptable salts of the subject compounds include the conventional nontoxic salts or quaternary ammonium salts of the compounds, e.g., from non-toxic organic or inorganic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, sahcyclic, sulfanihc, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isothionic, and the like.

In other cases, the compounds of the present invention may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically-acceptable salts with pharmaceutically-acceptable bases. The term "pharmaceutically-acceptable salts" in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in situ in the admmistration vehicle or the dosage form manufacturing process, or by separately reacting the purified compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically-acceptable metal cation, with ammonia, or with a pharmaceutically-acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base _>. addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, idiethanolamine, piperazine and the like (See, for example, Berge et al., supra). -

Wetting agents, emulsifiers and -lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents,-cσating- agents, sweetening, flavoring, and- . ^■'^■■ perfuming agents, preservatives and antioxidants can also be present in the compositions. Examples of pharmaceutically-acceptable antioxidants include: water soluble ..antioxidants, such as -ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and metal chelating agents, such as citric acid, ethylenediamine - tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Formulations of the present invention include those suitable for oral, nasal, topical

(including buccal and sublingual), rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well -known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, and the particular mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, this amount will range from about 1% to about 99% of active ingredient, preferably from about 5% to about 70%, most preferably from about 10% to about 30%. In certain embodiments, a formulation of the present invention comprises an excipient selected from the group consisting of cyclodextrins, liposomes, micelle forming agents, e.g., bile acids, and polymeric carriers, e.g., polyesters and polyanhydrides; and a compound of the present invention. In certain embodiments, an aforementioned formulation renders orally bioavailable a compound of the present invention.

Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.

Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, or as:.a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as - pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia)^" and/or as mouth washes-and the like, each containing a predetermined amount of a compound of the - present -invention as- an activeingredrerit A compound of .the present -invention may also be- administered as-a bolus, electuary or paste.

In solid-dosage forms of the invention for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), the active ingredient-is mixed with one or more - pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, maimitol, and/or silicic acid; binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; solution retarding agents, such as paraffin; absoφtion accelerators, such as quaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non-ionic surfactants; absorbents, such as kaolin and bentonite clay; lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and coloring agents, hi the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-shelled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made in a suitable machine in which a mixture of the powdered compound is moistened with an inert liquid diluent.

The tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and or microspheres. They may be formulated for rapid release, e.g., freeze-dried. They may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incoφorating sterilizing^agents.in the form of sterile -solid compositions that can l>e dissolved in sterile water, or some other sterile injectable medium mmediately before use. These compositions may also- optionallyicontain opacifying agents- and may be of aTcomposition that- they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in - micro-encapsulated form, if appropriate, with one or more of the above-described excipients.

Liquid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and- elixirs, hi addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, com, germ, olive, castor and sesame oils), glycerol, tefrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.

Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

Formulations of the pharmaceutical compositions of the invention for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or 5 more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound.

Formulations of the present invention which are suitable for vaginal administration also 10 include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are -known in the art to be appropriate.

Dosage forms for the topical or transdermal administration of a compound of this invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a 15 . pharmaceutically-aceeptable carrier, and with any ρreservatives,-buffers, or propellants wHch - •--••- may be required. - - ^■--- .

^~ - - - The-'bintments, pastes, creams and^gels may contain-, in- addition- tα an active compound - - of this invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, ^•- _ tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc an _. 0 -ziuc oxide, or mixtures thereof. . ^•" . ^,- -.

Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances.- Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. 25 Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Dissolving or dispersing the compound in the proper medium can make such dosage forms. Absoφtion enhancers can also be used to increase the flux of the compound across the skin. Either providing a rate controlling membrane or dispersing the compound in a polymer matrix or gel can control the rate of such flux. 30 Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention.

Pharmaceutical compositions of this invention suitable for parenteral administration comprise one or more compounds of the invention in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, 35 suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain sugars, alcohols, antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

Examples of suitable aqueous and nonaqueous carriers, which may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms upon the subject compounds may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbie acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the -^" compositions. addition, prolonged absoφtion of the injectable pharmaceutical form may be -^~- ^' brought about by the inclusion of agents which delay absoφtion such as aluminum monostearate and-g&latin.- ^■- -^~ --^■ - -- -- . - . - •-• - --...;- - "^■? ^• - ^: ~ -^■ '- . - -;-• _

In some cases, in order to prolong the effect of a drug, it is desirable to slow the absoφtion of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amoφhous material having poor water solubility. The rate of absoφtion of the drug then depends upon its rate of dissolution, which in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absoφtion of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions, which are compatible with body tissue.

In certain embodiments, a compound or pharmaceutical preparation is administered orally. In other embodiments, the compound or pharmaceutical preparation is administered intravenously. Alternative routs of administration include sublingual, intramuscular, and transdermal administrations. When the compounds of the present invention are administered as pharmaceuticals, to humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1% to 99.5% (more preferably, 0.5% to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier. The preparations of the present invention may be given orally, parenterally, topically, or rectally. They are of course given in forms suitable for each administration route. For example, they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administrations are preferred. The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrastemal injection and infusion. --'- " -^r ~ - . - - --.:- ._

The phrases "systemic administration," "administered systemically wperipheral - administration" and "administered peripherally" as usedherein.mean he administration o-f-a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

These compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally; parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. Regardless of the route of administration selected, the compounds of the present invention, which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically-acceptable dosage forms by conventional methods known to those of skill in the art.

Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present mvention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required to achieve the desired therapeutic effect and then gradually increasing the dosage until the desired effect is achieved. In some embodiments, a compound or pharmaceutical composition of the invention is provided to a synucleinopathic subject chronically. Chronic treatments include any form of repeated administration for an extended period of time, such as repeated administrations for one or more months, between a month and a year, one or more years, or longer, hi many embodiments, a chronic treatment involves administering a compound or pharmaceutical composition of the invention repeatedly-over the life of the synucleinopathic sub ect.¹ Preferred chronic treatments involve regular administrations, for example one or more firiles a day, one or more times a week, or one or-more timesTa month. In general, ^ra-suitable-dose suchaf a daily ^" dose of a compound of the invention will be that amount of the compound that is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Generally doses of the compounds of this invention for a patient, when used for the indicated effects, will range from about 0.0001 to about 100 mg per kg of body weight per day. Preferably the daily dosage will range from -0.001 to 50 mg of compound per kg of body weight, and even more preferably from 0.01^" to 10 mg of compound per kg of body weight. However, lower or higher doses can be used, hi some embodiments, the dose administered to a subject may be modified as the physiology of the subject changes due to age, disease progression, weight, or other factors.

If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. While it is possible for a compound of the present invention to be administered alone, it is preferable to administer the compound as a pharmaceutical formulation (composition) as described above.

The compounds according to the invention may be formulated for administration in any convenient way for use in human or veterinary medicine, by analogy with other pharmaceuticals. According to the invention, compounds for treating neurological conditions or diseases can be formulated or administered using methods that help the compounds cross the blood-brain barrier (BBB). The vertebrate brain [and CNS] has a unique capillary system unlike that in any other organ in the body. The unique capillary system has moφhologic characteristics which make up the blood-brain barrier (BBB). The blood-brain barrier acts as a system-wide cellular membrane that separates the brain interstitial space from the blood.

The unique moφhologic characteristics of the brain capillaries that make up the BBB are: (a) epithelial-like high resistance tight junctions which literally cement all endothelia of brain capillaries together, and (b) scanty pinocytosis or transendothelial channels, which are abundant in endothelia of peripheral organs. Due to the unique characteristics of the blood-brain barrier, hydrophihc drugs and peptides that readily gain access to other tissues in the body are barred from entry into the brain or their rates of entry and/or accumulation in the brain are very low.

In one aspect of the invention, farnesyl transferase inhibitor compounds that cross the BBB are particularly useful for treating synucleinopathies. In one embodiment, it-is expected that farnesyl transferase inhibitors that are non-charged-(e.g., not positively charged) and/or - noH-lipophilic may cross die BBB with higher efficiency than charged (e.g., positively charged) - and/or lipophilic compounds. Therefore it will be appreciated by a person of ordinary skill in the art that some of the compounds of the invention might readily cross the BBB. Alternatively, the -compounds of the invention can be modified, for example, by the addition of various substitutuents that would make them less hydropliilic and allow them to more readily cross the BBB.

Various strategies have been developed for introducing those drags into the brain which otherwise would not cross the blood-brain barrier. Widely used strategies involve invasive procedures where the drag is delivered directly into the brain. One such procedure is the implantation of a catheter into the ventricular system to bypass the blood-brain barrier and deliver the drag directly to the brain. These procedures have been used in the treatment of brain diseases which have a predilection for the meninges, e.g., leukemic involvement of the brain (US 4,902,505, incoφorated herein in its entirety by reference). Although invasive procedures for the direct delivery of drugs to the brain ventricles have experienced some success, they are limited in that they may only distribute the drag to superficial areas of the brain tissues, and not to the structures deep within the brain. Further, the invasive procedures are potentially harmful to the patient.

Other approaches to circumventing the blood-brain barrier utilize pharmacologic-based procedures involving drag latentiation or the conversion of hydrophihc drags into lipid-soluble drags. The majority of the latentiation approaches involve blocking the hydroxyl, carboxyl and primary amine groups on the drag to make it more lipid-soluble and therefore more easily able to cross the blood-brain barrier.

Another approach to increasing the permeability of the BBB to drugs involves the intra- arterial infusion of hypertonic substances which transiently open the blood-brain barrier to allow passage of hydrophihc drags. However, hypertonic substances are potentially toxic and may damage the blood-brain barrier.

Peptide compositions of the invention may be administered using chimeric peptides wherein the hydrophihc peptide drug is conjugated to a transportable peptide, capable of crossing the blood-brain barrier by transcytosis at a much higher rate than the hydrophihc peptides alone. Suitable transportable peptides include, but are not limited to, histone, insulin, transferrin, insulin-like growth factor I (IGF-I), insulin-like growth factor ?H (IGF-II), basic albumin and prolactin.

Antibodies are another method for delivery of compositions of the invention. For example; an antibody that is reactive with a transferrin receptor present on a brain capillary ----- endothelial cell, can-be conjugated to a neuropharmaceutical gent to produce an antibody- . neuropharmaceutical^" agent conjugate (US 5,004,697 incoφorated-lrerein in ts entirety by.- - reference). The method is conducted under conditions whereby the antibody binds to the -transferrin receptor on the brain capillary endothelial cell and the neuropharmaceutical agent is transferred across the blood brain barrier in a- pharmaceutically active form.- The uptake or transport of antibodies into the brain can also be greatly increased by cationizing the antibodies to form cationized antibodies having an isoelectric point of between about 8.0 to 11.0 (US 5 ,527,527 incoφorated herein in its entirety by reference) .

A ligand-neuropharmaceutical agent fusion protein is another method useful for delivery of compositions to a host (US 5,977,307, incoφorated herein in its entirety by reference). The ligand is reactive with a brain capillary endothelial cell receptor. The method is conducted under conditions whereby the ligand binds to the receptor on a brain capillary endothelial cell and the neuropharmaceutical agent is transferred across the blood brain barrier in a pharmaceutically active form. In some embodiments, a ligand-neuropharmaceutical agent fusion protein, which has both ligand binding and neuropharmaceutical characteristics, can be produced as a contiguous protein by using genetic engineering techniques. Gene constructs can be prepared comprising DNA encoding the ligand fused to DNA encoding the protein, polypeptide or peptide to be delivered across the blood brain barrier. The ligand coding sequence and the agent coding sequence are inserted in the expression vectors in a suitable manner for proper expression of the desired fusion protein. The gene fusion is expressed as a contiguous protein molecule containing both a ligand portion and a neuropharmaceutical agent portion.

The permeability of the blood brain barrier can be increased by administering a blood brain barrier agonist, for example bradykinin (US 5,112,596 incoφorated herein in its entirety by reference), or polypeptides called receptor mediated permeabilizers (R?MP) (US 5,268,164 incoφorated herein in its entirety by reference). Exogenous molecules can be administered to the host's bloodstream parenterally by subcutaneous, intravenous or intramuscular injection or by absoφtion through a bodily tissue, such as the digestive tract, the respiratory system or the skin. The form in which the molecule is administered (e.g., capsule, tablet, solution, emulsion) depends, at least in part, on the route by which it is administered. The administration of the exogenous molecule to the host's bloodstream and the intravenous injection of the agonist of blood-brain barrier permeability can occur simultaneously or sequentially in time. For example, a therapeutic drug can be administered orally in tablet form while the intravenous administration of an agonist of blood-brain barrier permeability is given later (e.g. between 30 minutes later and several hours later). This allows time for the drug to be absorbed in the gastrointestinal tract and taken up by the bloodstream before the agonist isrgiven to increase the permeability_.of thebiood-brain ^"barrier to the_;drug.--:On the other hand, antagonist of blood-brain barrier _ • • - - . permeability (e.g. bradykinin) can be administered before or at the same time as an intravenous injection of a drug. Thus, the term "co aφmnistration" is used herein to mean that the agonist of blood-brain barrier, and the exogenous molecule will be administered at times that will ach ve significant concentrations in the blood for producing the simultaneous effects of increasing the permeability of the blood-brain barrier and allowing the maximum passage of the exogenous molecule from the blood to the cells of the central nervous system.

In other embodiments,, compounds of the invention can be formulated as a prodrag with a fatty acid carrier (and optionally with another neuroactive drug). The prodrag is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The . prodrug passes readily through the blood brain barrier. The prodrag preferably has a brain penetration index of at least two times the brain penetration index of the drug alone. Once in the central nervous system, the prodrag, which preferably is inactive, is hydrolyzed into the fatty acid carrier and the farnesyl transferase inhibitor (and optionally another drug ) . The carrier preferably is a normal component of the central nervous system and is inactive and harmless. The compound and/or drug, once released from the fatty acid carrier, is active. Preferably, the fatty acid carrier is a partially-saturated straight chain molecule having between about 16 and 26 carbon atoms, and more preferably 20 and 24 carbon atoms. Examples of fatty acid carriers are provided in US Patent Nos. 4,939,174; 4,933,324; 5,994,932; 6,107,499; 6,258,836 and 6,407,137, the disclosures of which are incoφorated herein by reference in their entirety.

The administration of the agents of the present invention maybe for either prophylactic or therapeutic pvupose. When provided prophylactically, the agent is provided in advance of disease symptoms such as any Alzheimer's disease symptoms. The prophylactic administration of the agent serves to prevent or reduce the rate of onset of symptoms. When provided therapeutically, the agent is provided at (or shortly after) the onset of the appearance of symptoms of actual disease. In some embodiments, the therapeutic administration of the agent serves to reduce the severity and duration of Alzheimer's disease.

The function and advantage of these and other embodiments of the present invention will be more fully understood from the examples described below. The following examples are intended to illustrate the benefits of the present invention, but do not exemplify the full scope of the invention.

EXAMPLES

Experimental Procedures

Tissue culture: All cell lines were obtained by ATCC. SH-SY5Y and Cos-7. were grown in 10% FBS D?MEM (Sigma). Cells were split the day before experiments. including - , transfection, metabolic labeling and drug treatment.

Proteins and antibodies: UCH-Ll variants were purified according to the published procedure. Synuclein antibody (SYN-1) was purchased from Signal Transduction Lab. Actin antibody and FLAG antibody (M2) were from Sigma. UCH-Ll antibody (anti-PGP 9.5) was from Chemicon.

Chemicals: FTI-277 and lactacystin was purchased from Calbiochem. Crosslinking reagent DE was from Pierce. DMEM and MEM were purchased from Gibco. All the other material was purchased from Sigma.

Plasmids: C220S cDNA was generated by PCR site-specific mutagenesis. For the PCR, the 5' primer is uchforw SEQ ID NO: 1 (CTAAAGCTTATGCAGCTCAAGCCGA TGGAG), and 3' primer is uchc220s SEQ ID NO: 2 (CTAAGACTCG

AGTTAGGCTGCCTTGCTGAGAGC). Wt UCH-Ll served as the template. The PCR fragment was inserted into pcDNA vector. For S18YC220S mutant, S18Y UCH-Ll served as the template in PCR. For the FLAG tagged UCH-Ll, the 5' primer is FLAGuchforw SEQ ID NO: 3 (CTAAAGCTTATGGACTACAAGGA TGACGACGACAAAGATGCAGCTCAAGCCGATGGAG), and the 3' primer is uchrev SEQ ID NO: 4 (ATCCTCGAGTTAGGCTGCCTTGACGAGAGC). Wt UCH-Ll or C220S served as the template. PCR fragment was purified and inserted into pcDNA vector. For the FLAG tagged UCH-L3, the 5' primer is L3Hindiπ SEQ ID NO: 5 (CTAAAGCTTATGGACTACAAGGATGACGACGACAAAGATGGAGGGTCAACGCTGG CTG), the 3'primer is L3?XhoISAA SEQ ID NO: 6 (ATCCTCGAGCTA TGCTGCAGAAAGAGCAATCGCA). For the UCH-L3 CKAA variant, the 5' primer is L3 Hindlll and the 3 ' primer is L3XhoICKAA SEQ ID NO: 7 (ATCCTCGAGCTATGCTGCCTTAGAAAGAGCAATCGCATTAAATC). α-synuclein degradation assay: Liphitamine 2000 was used to transfect COS-7 cells according to the Invitrogen protocol. Transfected cells were cultured at 37 °C for 48 hours before being treated with 35 μM lactacystin or DMSO. After 24 hours of incubation, the cells were lysed with Tris buffer (50 mM Tris, 2% SDS, 0.1% NP-40), and subjected to SDS-PAGE/ followed by quantitative Western blotting. Salt and detergent treatment of-SV fraction: SV fraction-was prepared as describe elsewhere. SV was incubated with various salts' at designed concentration for 30 minutes on ice, or 1% Triton X-100 or control without salts and detergent.- Treated SV waέrpelleted at-100,000g for 30 ^r - ^" minutes. Supernatants and pellets were subjected to SDS-PAGE and Western blotting.

Membrane fractionation: Cells were harvested by scraping and washed with PBS. Cell pellet was suspended in lysis buffer (50mM Tris-HCl, ImM EDTA) supplemented with protease inhibitor cocktail (Sigma) and homogenized bypassing through 26G needles 10 times. Suspension was clarified by spinning at 600g for 5 minutes. Clarified suspension was ultracentrifugdd at 100,000g for 2 hours and separated into membrane and cytosol. Membrane fraction was washed with washing buffer (50mM Tris-HCl, ImM EDTA 1M NaCl), and pelleted each time with bench-top centrifuge.

2D electrophoresis: For the isolation of total cellular protein, cultured SH-SY5Y cells maintained as described above were rinsed with ice-cold PBS. Cells were lysed in 1ml dSDS buffer (50mM Tris-HCl, pH 8.0 0.1% SDS) supplemented with protease inhibitor cocktail. Lysates were boiled for 3 min, and were treated with Dnase and Rnase as described. Lysates were precipitated with ice-cold acetone for at least 2 hours, and pellets were resuspended in 2D sample buffer (8M urea, 0.5% CHAPS, 0.2% DTT, 0.5% IPG buffer, 0.002% bromophenol blue).2D electrophoresis was carried out according to manufacture's protocol (Amersham Life Science). 7cm pH 4-7 strips were used. For SH-SY5Y membrane fraction, culture SH-SY5Y cells were rinsed with cold PBS and harvested with lysis buffer (50mM Tris-HCl, pH 8.0, ImM ZnAc2, 250mM sucrose). Lysate was passed through 25G needles for several times and spun at lOOOg for 5 min. Supernatant was centrifuged at 200,000g for 2 hours. Pellet was extensively washed with lysis buffer and extracted with cold acetone. Pellet was resuspended in 2D sample buffer.

Viral Infection: Viral infection and MTT -assay in SH-SY5Y cells: The viruses were amplified and purified according to the published procedure. SH-SY5Y cells were grown on 100mm petri-dishes and induced with lOOnM RA for 3-5 days before the virus infection with M.I.O at 75. Viruses were diluted with DPBS to desired M.I.O.. After four hours of incubation, 10ml growth medium was added. On the second day, cells were splitted into 96-well plates and treated with compounds for next 48 hours. The growth medium in each well was replaced with growth medium with 5ug/ml MTT. Medium was removed after three hours incubation, and 200ul isopropyl (0.04N HC1) was added into each well. The signal was read at 570nm.

Viable cell counting: At stated time poins, SH-SY5Y cells were trypsinized with lOOul trypsin-EDTA for 1 minute and neutralized with 400ul growth medium. Cell suspension was made up by mixing 0.2 ml of cells in growth medium, 0.3 ml of HBSS and 0.5 ml of 0.4% Trypan Blue, solution. Viable cell- numbers were counted by standard cell counting chamber.. Western Blotting: Following transfer of SDS gels onto NC membrane, all membranes - were blocked with 5% non-fat milfeiή TBST (50mM Tris-HCl pH74, 15QmM-NaCl, 0.1% -- • -- Tween 20), and incubated with primary antibody overnight with 1% BSA in TBST, washed three times vith TBST, and incubated with horseradish peroxidase_rconjugated secondary antibody for 1 hour (Promega). Bound antibodies were detected using enhanced chemiluminascence (NE?M).

Example 1: UCH-Ll is famesylated in vivo and in cell culture

The UCH-Ll sequence contains the sequence CXXX, a consensus farnesylation site, at its C-terminus. This sequence is not present in UCH-L3. The possibility that this sequence was modified in vivo was investigated. First, the chemical nature of the previously reported association of UCH-Ll and synaptic vesicles from rat brain was probed. The results are shown in Figure 1, panel (A): Effects of various amount of salt and non- ionic detergent on the dissociations of synapsin I, synaphysin and UCH-Ll from SV was analyzed by treating aliquots of SV fraction with either KC1, NaCl, MgCl₂, or 1% Triton X-100. Membrane fraction and soluble fraction was separated by centrifugation and each fraction was subjected to SDS-PAGE followed by Western blots, a (synapsin I), c (synaphysin) and e (UCH- LI) are from pellet, and b (synapsin I), d (synaphysin) and f (UCH-Ll) are supernatant fractions. Unlike synapsin (Figure 1, panel A, rows a and b), which is not an integral membrane protein, and like synaptophysin (rows c and d), UCH-Ll (rows e and f) could not be separated from the vesicular fraction by increasing salt concentration. Only treatment with detergent was sufficient to solubilize UCH-Ll, consistent with its farnesylation. 5 Analysis of various fractions from SH-SY5Y neuroblastoma cells (similar results from rat brain, not shown) by two-dimensional SDS-PAGE gel electrophoresis showed two major and two minor species in the total homogenate and one species in the membrane-associated fraction (Figure 1 panel (B): More than 2 forms of UCH-Ll were present in SH-SY5Y cell (gel a) detected using 2D electrophoretic analysis followed by Western blotting. Only one of them

10 (open arrow) is associated with membrane (gel b). Treatment of SH-SY5Y cells with FTI-277 (gel d) results in a significant decrease in the amount of membrane bound UCH-Ll (open arrow) without affecting the amount of cytosolic UCH-Ll (close arrow) when compared to cells treated with DMSO (gel c). This species was presumably the fully processed species: famesylated, truncated and C-terminally methylated.

15 Consistent with-this premise, treatment of the cells withthe farnesyl transferase inhibitor

FTI-277 decreased-the amount of the membrane-associated species, hi addition, a UCH-Ll -

- v- . containing species wasimmunoprecipitated from. whole cell lysate-by-an anti-fafnesyl antibos-y . (Calbiochem). Finally, treatment of the cells with 14G-mevalonic acid or with 3H-farnesol . resulted in incoφoration of radiolabel into UCH-Ll (Figure 1, panel (C)). UCH-Ll was

20 modified with _,[¹⁴G] mevalonate. (gel a) and [³H] famesol (gel b) in vivo. (b). .Transfection.of the C220S mutant into COS-7 cells prevented radioincoφoration and eliminated the membrane- . associated species (not shown). Figure 1, panel (D), shows that WT UCH-Ll but not the C220S variant was detected in the membrane fraction of COS-7 cells transfected with either of the UCH-Ll variants).

25

Example 2: Removal of the farnesyltation site has no effect on the in vitro enzymatic activity or aggregation properties of UCH-Ll

The C220S mutant as expressed in E. coli and purified using a published method. As 30 expected from examination of structural models of UCH-Ll, the point mutation had no effect on the in vitro hydrolase (Figure 2, panel A) or ligase (panel B) activities. (A) Michaelis-Menten plot of various amount Ub-AMC titrated against either UCH-Ll WT (close circle) or C220S (open circle) showed comparable hydrolytic activities. (B) The mutation does not affect UCH- Ll in vitro ligase activity. In addition, the C220S mutation did not eliminate the propensity of S18 to oligomerize. This finding cleared the way to examine the effects of C220S in cell culture.

Example 3: Farnesylation and membrane association of UCH-Ll is required to promote accumulation of α-synuclein in COS-7 cells.

The C220S mutation eliminated the ability of SI 8 to promote α-synuclein accumulation in COS-7 cells but had no effect on the S18Y polymoφh (Figure 2, panel (C): the relative amount of 16kDa α-synuclein was quantified and normalized against the amount of actin in transfected COS-7 cells with the presence of UCH-Ll variants. 100% accumulation of α- synuclein was achieved in cells treated with proteasome inhibitor lactacysteine). This finding suggested that farnesylation and membrane attachment of UCH-Ll are both required. In order ^• to isolate the latter possibility, a mutant form of UCH-L3 was constructed in which the UCH-Ll - farnesylation sequence was added to the UCH-L3 C-terminus. This protein did not cause - accumulation of α-synuclein (panel (D) The relative amoun ofα-"synuclein was compared ■- among COS-7 cells transfected with UCH-Ll and UCH-L3 variants), althoughit was . famesylated-and incoφørated into the membrane (not shown). This, membrane attaehment of an active hydrolase was insufficient to cause accumulation of α-synuclein.

Example 4: Inhibition of farnesylation rescues cell death caused by α-synuclein overexpression in SH-SY5Y cells.

Since α-synuclein neurotoxicity is dose-dependent, it follows that accumulation of α- synuclein, caused by UCH-Ll farnesylation, should promote its toxicity. We demonstrated this to be true in mamallian neuroblastoma SH-SY5Y cells. This dopaminergic cell line has been used to demonstrate the rescue of α-synuclein toxicity by parkin, an effect that has also been demonstrated in primary dopaminergic cultures. These cells express high endogenous levels of UCH-Ll. The α-synuclein gene was overexpressed (as compared to endogenous levels) via infection with an adenoviral vector and toxicity was demonstrated by the Trypan blue (Figure 3) and MTT assays (Figure 4). ^• Figure 3 shows SH-SY5Y cells infected by α-synuclein-expressing adenovirus treated with DMSO (A), FTI-277 (B), LDN57414 (C), FTI-277 and LDN57414 (D) . (E) Viable cell numbers were quantified by counting the cells treated with either DMSO (lower dark circles), FTI-277 (upper dark circles), LDN57414 (light triangles) or LDN57414 and FTI- 277 (dark triangles) that did not stain with trypan blue. The unit of y-axis is 10⁵/ml. (F) Cell viability was assessed by the amount of metabolic activity using MTT assay. Figure 4 shows: (A) the viability of SH-SY5Y cells infected by α-synuclein-expressing adenoviras after treatment of DMSO (closed triangles) or FTI-277 (open triangles), and of cells infected with lacZ-expressing adenovirus after treatment of DMSO (closed circles) or FTI-277 (open circles), and of cells infected with empty adenoviras after treatment of DMSO (closed squares) or FTI- 5 277 (open squares) were assessed using MTT assay. The effect of FTI-277 on the α-synuclein accumulation in the SH-SY5Y infected with α-synuclein-expressing adenovirus were analyzed by Western blotting (B) and the amount of α-synuclein (C) was quantified using ?N?IH Image program and normalized against the amount of actin. The commercially-available small molecule farnesyl transferase inhibitor FTI-277, which had 0 previously been shown to reduce the amount of membrane-associated, famesylated species

(Figure 1, panel B, row d), resulted in a significantly decreased loss of cells (compare Figure 3, panel B to panel A). This neuroprotective effect was eliminated by co-adminstration of the small-molecule UCH-Ll inhibitor (not shown), suggesting that the FTI effect was primarily due to its effect on UCH-Ll. Treatment with FTI-277 reduced the total amount of UCH-Ll in SH- 5 S-Y5Y cells and increased its^' rate ofttimover (pulse-chase experiment not shown), in addition to i educing the amount of membrane-associated protein. This treatment also reduced the amount ^•

- ^■-^• - ofα-syπuclehr-in-these cells {Figure 4, -panels B and G). ^{" '}- ^■'' ^{' r} - - ^r- ^•- ^• ■^•> -

The following patent publications describe useful farnesyl transfease inhibitor 0 , compounds, their structural and functional analogs and.compositions and related synthetic methods: WO 2003041658, WO 2002085819, WO 2001072721, WO 2000042849, WO 2003076660, WO 2002080895, WO 2002072085, WO 2002056884, WO 9730992, WO 9901434, US 2003162965, US 2002169313, US 2002002162, US 6537988, US 2003134846, US 2003073677, US 2003092705, US 6645966, US 6011029, US6387926, US6602883, 5 US6455523. The disclosures of these and all patents, patent publications and scientific publications are incoφorated by reference herein in their entirety.

Having now described some illustrative embodiments of the invention, it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting,

30 having been presented by way of example only. Numerous modifications and other illustrative embodiments are within the scope of one of ordinary s?kill in the art and are contemplated as falling within the scope of the invention. In particular, although many of the examples presented herein involve specific combinations of method acts or system elements, it should be understood that those acts and those elements may be combined in other ways to accomplish the same

35 objectives. Acts, elements and features discussed only in connection with one embodiment are not intended to be excluded from a similar role in other embodiments. Further, for the one or more means-plus-ftmction limitations recited in the following claims, the means are not intended to be limited to the means disclosed herein for performing the recited function, but are intended to cover in scope any means, known now or later developed, for performing the recited function. Use of ordinal terms such as "first", "second", "third", etc., in the claims to modify a claim element does not by itself connote any priority, precedence, or order of one claim element over another or the temporal order in which acts of a method are performed, but are used merely as labels to distinguish one claim element having a certain name from another element having a same name (but for use of the ordinal term) to distinguish the claim elements. Similarly, use of a), b), etc., or i), ii), etc. does not by itself connote any priority, precedence, or order of steps in the claims. Similarly, the use of these terms in the specification does not by itself connote any required priority, precedence, or order.

The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the invention. The present invention is not to be limited in scope by examples provided, since=the examples. are intended as a.single illustration of one,aspect of the invention and other functionally equivalent embodiments are within the scope of the invention. Various modification serf the mvention in- addition to those shown an described herein will become?- . apparent to those skilled in the art from the foregoing description and fall within the scope of the appended claims. The advantages and objects_pf the invention are not necessarily encompassed by each embodiment of the mvention. _. ■ ; =■- -..

We claim:

Claims

1. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula:

II πi

IV or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherem m,n,r,s and t are 0 or 1; p is 0, 1 or 2;

V, W and X are selected from the group consisting of oxygen, hydrogen, R¹, R² or R³;

Z and Y are selected from the group consisting of CHR⁹, S0₂, S0₃, CO, C0₂, O, NR¹⁰, SO₂

NR¹¹, CONR¹²,

O

-C- -O S N N ~ O NR²⁰ R²¹N NR²²

R 16 R"

or Z may be absent;

P is.⁶ , P is⁷ , P ts\⁹ , t Ps.¹⁰ , PJ\-¹¹ , P is.¹² , Pis.¹³ , P is.¹⁴ , P is.¹⁵ , P is.¹⁶ , P is.¹⁷ , P is.¹⁸ , P is.¹⁹ , P is.²⁰ , i Ps.²¹ , P is.²² , i Ps.²⁴ , P is.²⁵ , P is.²⁶ , P Jtv²⁷ , P is.²⁸ ,

R²⁹, R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl;

R⁴, R⁵ are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R²³ ; U is selected from the group consisting of sulfur, oxygen, ?NR²⁴, CO, SO, S0₂, C0₂,.?NR²⁵ C0₂,

NR²⁶ CONR²⁷, NR²⁸ S0₂, NR²⁹ S0₂ NR³⁰, S0₂ N , NR³?² CO, CONR³³, P0₂ R³⁴ and-P0₃.

R³⁵ or U is absent;

R¹, R², and R³ are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, carboxy, carbamyl (e.g. CO-NH₂) or substituted carbamyl further selected from CO- H alkyl, CO?NH aryl, CO?NH aralkyl or cases where there are two substituents on the nitrogen selected from alkyl, aryl or aralkyl; R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;

Any two of R¹, R², and R³ can be joined to form a cycloalkyl group;

R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)pQ wherein Q is

NR³⁶ R³⁷, OR³⁸, or CN; and

A, B, C and D are carbon, oxygen, sulfur or nitrogen. with the provisos that

1. When m is zero then V and W are not both oxygen or

2 W and X together can be oxygen only if Z is either absent, O, ? R¹⁰, CHR⁹,

in formulas I and II, and V and X together can be oxygen only if Y is O, ? R 10 , CHR^'

in formulas IH and IV or 3. R²³ maybe hydrogen except when U is SO, S0₂, NR²⁵ C0₂ or

NR²⁸ SO₂, or

4. R⁸ may be hydrogen except when Z is S0₂, C0₂, or

2. The method of claim 1, wherein the famesyl transferase inhibitor compound is of the formula:

π

wherein m is 0; n is 1 and r, s and t are 0 or 1; p is 0, 1 or 2;

V, W and X are selected from the group consisting of oxygen, R¹, R² and R³

Z and Y are selected from the group consisting of CHR^y, S0₂, S0₃, CO, C0₂, O, NR 10 , S0₂

NR^π, CONR¹², 0

or Z may be absent;

P is⁷ , P is.⁹ , P is.¹¹ , P is.¹² , P is.¹³ ,

P is.¹⁵ , P is.¹⁶ , P is.¹⁷ , P is.¹⁸ , P is.¹⁹ , P is.²⁰ , P is.²¹ , P is.²² , P is.²⁴ , P is.²⁵ , P is.²⁶ , i Ps.²⁷ , P is.²⁸ , P is.²⁹ ,

R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷ and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl, or substituted aryl;

R⁴ and R⁵, are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R²³ ; U is selected from the group consisting of sulfur, oxygen, ?NR²⁴, CO, SO, S0₂, C0₂, ?NR²⁵

C0₂, NR²⁶ CONR²⁷, NR²⁸ S0₂, NR²⁹ S0₂ NR³⁰, S0₂ NR³¹, NR³² CO, CONR₃₃, P0₂ R³⁴, and

P0₃ R³⁵ or U is absent;

R¹, R², and R³ are selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, hetercyclo, substituted heterocyclo, cyano, carboxy, carboxy, carbamyl or substituted carbamyl;

R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R¹, R², and R³ may be joined to form a cycloalkyl group;

R, S, and T are selected from the group consisting of CH₂, CO and CH(CH₂)pQ wherein Q is NR³⁶ R³⁷, OR³⁸, or CN; and

A, B, C and D are carbon, with the provisos that

1. When m is zero then V and W are not both oxygen or

2. W and X together can be oxygen only if Z is either absent, O, NR¹⁰, CHR⁹,

in formula II, and V and X together can be oxygen only if Y is O, ?NR¹⁰, CHR⁹,

in formula IV or

3. R²³ maybe hydrogen except when U is SO, S0₂, NR²⁵ C0₂ or NR²⁸ S0₂, or

4. R⁸ maybe hydrogen except when Z is S0₂, C0₂, or

3. The method of claim 1, wherein the compound is selected from the group consisting of:

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

8-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-4-(lH-imidazol-4-yl-methyl)-l-(l-l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; 2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-yl-methyl)-2-methyl-4-(l -naphthalenylcarbonyl)- 1 -H-

1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-4-(l-naphthalenylcarbonyl)-l-[[l-(phenylmethyl)-lH-imidazol-5- yl]methyl]-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-(lH-imidazol-4-yl-methyl)-4-(l -naphthalenylsulfonyl)- 1 H- 1 ,4- benzodiazepine, hydrochloride;

(S)-2,3,4,5-Tefrahy(ho-l-(lH-imidazol-4-yhnethyl)-3-[2-(nrethylthio)ethyl]-4-(l- naphthalenylcarbonyl)-lH-l,4-benzbdiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)^N-methyl-N-phenyl-4H-l,4- ^" benzodiazepine-4-carboxamide, hydrochloride; 2-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-lH-l,4-benzodiazepin-4- yl]sulfonyl]benzoic acid, methyl ester, hydrochloride;

1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenenylcarbonyl)-7-phenyl-lH- 1,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahy(ho-l-(lH-imidazol-2-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-[3-(lH-imidazol-2-yl)propyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[3-Amino-3-(lH-imidazol-2-yl)propyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, trihydrochloride;

1,4-benzodiazepine, hydrochloride; ■ (S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; 2,3,4,5-Tefrahy(fro-l-(lH-in-ύdazol-4-y-lmemyl)-9-memyl-4-(l-naph alenylcarbonyl)

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-(lH-imidazol-4-ylmethyl)-9-methyl- 1 -(1 -naphthalenylcarbonyl)- 1H-

1,4-benzodiazepine, dihyrdochloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-lH-l ,4-benzodiazepine, trihydrochloride; l-[[2-Aminomethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)- IH- 1 ,4- benzodiazepin-8-yl]acetamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-nitro-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naphmalenylcarbonyl)-8-amino-lH-

1,4-benzodiazepine, dihydrochloride; N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]benzamide, dihydrochloride;

N-[2,3,4,5-Tefrahycho-l-(lH-irmdazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride; ^" - -

2,3,4,5-Tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naρhthalenylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazeρine, dihydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihydrochloride; l-[[l-(2-Aminoethyl)-lH-imidazol-5-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine-4- carboxylic acid, phenylmethyl ester;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-y-Lmemyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]- lH-l,4-benzodiazepine;

1 ,2,3,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- 1 ,4- benzodiazepine-4-carboxamide, dihydrochloride;

2,3,4,5,-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaleneylcarbonyl)-7-(l- piperidinylsulfonyl)- IH- 1 ,4-benzodiazepine, monohydrochloride; 2,3,4,5-Tefrahydro-l-(lH-inύdazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-pyridin-2-yl- lH-l,4-benzodiazepine, trihydrochloride;

7-(2-Furanyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)- lH-l,4-benzodiazepine, dihydroc-hloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-7-(2-thienyl)- lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-7-(4-pyridinyl)-

1H-1 ,4-benzodiazepine, trihydrochloride;

1,4-benzodiazepine, dihydrochloride;

8-CUoro-2,3,4,5-tefrahydro-4-(lH-irnidazol-4-ylmethyl)-l-(l-naphthalenylcarbonyl)-lH-

1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-4-(lH-imidazol-4-ylmethyl)-l-(l-naphthalenylcarbonyl)-7-phenyl-lH-

1 ,4-benzodiazepine, hydrochloride; 2;3,4,5-Tetrahydro-l ,4-bis(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylmethyl)-7-phenyl-lH-i,4- benzodiazepine, trifluoroacetate; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-methoxy-4-(l-naphthalenylcarbonyl)-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-5-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-cyclohexyl- lH-l,4-benzodiazepine, 2.5 hydrochloride;

7-Butyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydroc-hloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride; l-[[2-(Aιninomethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l- naphthalenylcarbonyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)-8-[N,N- bis(phenyl-methyl)amino]-lH-l,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]phenylsulfonamide, dihydrochloride; N-Phenyl-2,3,4,5-tefrahy(ho-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-

1 ,4-benzo-diazepine-7-carboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-methylbenzamide, dihydrochloride; N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-4-methylbenzamide, dihydrochloride;

3-CUoro-N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l -naphthalenylcarbonyl)- lH-l,4-benzo-diazepin-8-yl]benzamide, dihydrochloride;

7-Bromo-2,3,4,5,-tetrahydro-l-[[2-[(dimethylamino)-methyl]-lH-imidazol-4-yl]methyl]-4- (l-naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-(4-Chloroρhenyl)-2,3,4,5-tefrahydro-l-(lH--u-nidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-(3-Anmιoρhenyl)-2,3,4,5-tefrahydro-l-(lH-hnidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride; l-Memyl-N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepin-8-yl]-lH-pyrrole-2-cafboxamide, trihydrochloride;

N-[2,3 ,4,5-Tetrahydro- ϊ -( lH-imidazol-4-ylmethyl)-4-( 1 -naphthalenylcarbonyl)- 1 H- 1 ,4- benzddiazepin-8-yl]-3-furahcarboxamide, dihydrochloride;

7-(3-Chloroρhenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1 H-l ,4-benzodiazepine, dihydrochloride;

2-Methyl-N-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)

1H-1 ,4-benzodiazepin-8-yl]benzamide, dihydrochloride;

N-Phenyl-N'-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)- lH-l,4-benzodiazepin-8-yl]urea, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-(3-pyridinyl)- lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-9-methoxy-4-(l-naphthalenylcarbonyl)-lH-

1,4-diazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-3-(2-hydroxyethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, trifluoroacetate; 2,3,4,5-Tetrahydro-4-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaIenylcarbonyl)-3-

(phenylmethyl)-l H-l ,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tefrahy(ho-4-(lH-imidazol-4-yhnethyl)-l-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, 1.5 hydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-7-phenyl-3-(phenylmethyl)-lH-

1,4-benzodiazepine, trifluoroacetate; 4-Acetyl-7-bromo-3-[(4-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-lH- 1,4-benzodiazepine, dihydrochloride; ^~

N-Cyclohexyl-N'-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthaienylcaibonyl)-lH-l,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,2-Dimethyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepin-8-yl]propanamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylsulfonyl)-7-phenyl-lH-

1,4-benzodiazepine, monohydrochloride;

4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(2- naphthalenylmethyl)-lH-l ,4-benzodiazepine, dihydrochloride; 4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(l- naphthalenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-(2-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, monohydrochloride; l-Methyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, trihydrochloride;

N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-4-moφholinecarboxamide, dihydrochloride; N-[2,3,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(l -naphthalenylcarbonyl)- IH- 1 ,4- benzodiazepin-8-yl]-3-methylbutanamide, dihydrochloride; l,2,3,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-N,N,7-triphenyl-4H-l,4-2 5 benzodiazepine-4-carboxamide, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(4-phenyl-l,2,3-thiadiazol-5- yl)carbonyl]- IH- 1 ,4-benzodiazepine, trifluoroacetate;

8-[[(Cyclohexyla-D-ύno)carbonyl]amino]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxylic acid, 1,1-dimethylethyl ester;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3- (phenyhnethyl)-lH-l,4-benzodiazepine-4-carboxylic acid, 1,1-dimethylethylester;

7-Bromo- 1 ,2,3,4-tetrahydro-l -(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-5H- 1 ,4- benzodiazepin-5-one, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[l-oxo-3-(l-piperidinyl)propyl]-7-phenyl-

IH- 1,4-benzodiazepine, trihydrochloride; 2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)- 1 H- 1 ,4- benzodiazepine, trihydrochloride; -

4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-beήzodiazepine, trihydrochloride;

(S)-4-[2-(Dimemylamino)-l-oxo-3-phenylpropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-ρhenyl-lH-l,4-benzodiazeρine, trihydrochloride;

2,3,4,5-Tetrahydro-4-[4-hy(hoxy-3-(4-moφholinyl-methyl)benzoyl]-l"(lΗ-imidazol-4- ylmethyl)-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

(S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-2-pyrrolidinyl)carbonyl]-

7-phenyl-lH-l ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetτahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(proρylthio)-3- pyridinyl] carbonyl] - 1 H- 1 ,4-benzodiazepine, trihydrochloride;

4-[(2-Chloro-6-methyl-4-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(phenylthio)-3- pyridinyl]carbonyl]-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4-methylρhenoxy)-3- pyridinyl] carbonyl] -7-phenyl- 1 H- 1 ,4-b enzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylrnethyl)-7-phenyl-4-[(5-phenyl-4- oxazolyl)carbonyl]-lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-irm^azol-4-y-lmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-3- furanyl)carbonyl]-lH-l ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3 ,4,5 -Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-4- [4-(4-moφholinylmethyl)benzoyl] -7- phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-ρhenyl-

1H-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[l-oxo-3-(phenylsulfonyl)propyl]-7- ρhenyl-lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridinylacetyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3 ,4, 5 -Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)- 1 H-

1 ,4-behzodiazepine, tetrahydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(4-isoquinolinylcarbonyl)-7-phenyl-H- 1,4-benzodiazepine, trihydrochloride;

4-[(2-Chloro-3-ρyridittyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4_^ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridmylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 4-[(2,6-Dimethoxy-3-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

4-(2-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[3-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7 -phenyl- lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(l- phenylcyclopropyl)carbonyl]-lH-l,4-benzodiazepine, dihydrochloride; 4-[(Bicyclo[4.2.0]octa-l,3,5-toen-7-yl)carbonyl]-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4- ylmethyl)-7-ρhenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-Benzoyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride; 4-(2-Chlorobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

N-[2-[[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazeρin-4- yl]carbonyl]phenyl]-acetamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(2,3-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl_rlH-l,4- benzodiazepine, dihydrochloride;

4-(2,4-Dimethoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-inndazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,5-Dime oxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-in-ndazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,6-Dimethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-~ benzodiazepine, dihydrochloride;

4-(2,3-Dihydroxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-([l,r-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3-Chlorobenzoyl)-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-y-hnethyl)-4-(3-methoxybenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(3,4-Dimemoxybenzoyl)-2,3,4,5-tefrahyάιo-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3,5-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(l,2-Dioxo-2-ρhenylethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

4-[(2-Ethoxy-l-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

4-(Fluorophenylacetyl)-2,3,4,5-tefrahydro-l-(lH-iιm^azol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(piphenylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-(2-hydroxy-l-oxo-2-phenylpropyl)-l-(-lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-2-ylcarbonyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-3-ylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-mdol-5-ylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-lH-indol-2-yl)carbonyl]-7- phenyl- IH- 1,4-benzodiazepine, dihydrochloride;

4-(2-Benzofuranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-pyridinylcarbonyl)-lH-l,4- benzodiazepine, N-oxide, dihydrochloride; 2,3,4,5-Tefrahy(-ho-l-(lH-inudazol-4-ylmethyl)-7-ρhenyl-4-(2-pyridinyϊcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(l-isoquinolinylcarbonyl)-lH-

1,4-benzodiazepine, trihydrochloride;

4-(3-Chloro-2-nitrobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(2-nitrobenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitτόbenzoyl)-7-phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-4-ylcarbonyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride; 4-[(2,6-Dihydroxy-3-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethjl)-7-phenyl-lH- 1,4-benzodiazepine, dihydrochloride;

4-(lH-Benzimidazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH- 1,4-benzodiazepine, trihydrochloride;

4-(lH-Benzotriazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- 1-H- 1,4-benzodiazepine, dihydrochloride;

2,3₃4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-[(4-memoxy-2-qu olinyl)c--u-bόnyl]-7- ^■ . phenyl- IH- 1 ,4-benzodiazepine, trihydrochloride;

N-[3-[[2_;,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH ,4-benzodiazepia-4- yl] carbonyl]phenyl] -acetamide, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxo-2-ρhenylρroρyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-[2-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-

1H-1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-4-(2-hydroxy[l,l *-biphenyl]-3-ylcarbonyl)-l-(lH-imidazol-4-ylmethyl)-

7-phenyl- IH- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxy-l-naρhthalenyl)carbonyl]-7- phenyl-lH-l,4-benzodiazepine, dihydroc-hloride;

2,3,4,5-Tefrahydro-4-[(2-hyάϊoxy-4-quinolinyl)-carbonyl]-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride; 2-[[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]benzamide, dihydroc-hloride;

N-(l,l-Dimethylethyl)-2-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl] carbonyl]benzamide, dihydrochloride;

N-(4-Fluorophenyl)-N'-[3-[[2,3,4,5-tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH- l,4-benzodiazepin-4-yl]carbonyl]phenyl]urea, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H- benzopyran-8-yl)carbonyl]-7-phenyl-lH-l,4-be:nzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[3-(trifluoromethoxy)benzoyl]-

IH- 1,4-benzodiazepine, dihydrochloride; 4-(2-Cyanobenzoyl)-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[[(4- methylphenyl)sulfonyl] aminojbenzoyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l -(lH-imidazol-4-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)- 1H-1 ,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tetτahycho-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)-lH ,4- benzodiazepine, trihydrochloride;

4-(Benzo[b]ibiophen-2-ylcari3onyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride; 4-[[4-(Dimethylamino)-l-naphthalenyl]carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(lH-purin-6-ylcarbonyl)-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetτahydro-l-(lH-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(5-methyl-l-phenyl-lH-pyrazol-4- yl)carbonyl]-7-phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)-l-oxopropyl]-7- phenyl-lH- 1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-4-ρhenyl-2H- pyran-4-yl)carbonyl]-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-iιnidazol-4-ylmethyl)-4-[2-(methylρhenylamino)benzoyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(4-q nolinylcarbonyl)-lH-l,4- benzodiazepine, N-oxide, dihydrochloride;

N-Methyl-N-(2-pyridinyhτιethyl)-2-[[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-1 ,4-benzodiazepin-4-yl]carbonyl]benzamide, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-4-(3 -isoquinolinylcarbonyl)-7-phenyl- 1 H- 1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-inύdazol-4-ylmemyl)-4-[(2-naphmalenyltHo)acetyl]^ benzodiazepine, trifluoroacetate (1:2);

4-[3-(3,4-Dimemoxyphenyl)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)- lH-l,4-benzodiazepine, trifluoroacetate (1:2); 4-([l , 1 ^,-Biρhenyl]-4-ylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l ,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naρhthalenylacetyl)-lH-l,4- benzodiazepihe trifluoroacetate (1 :2); ^"

4-([l,l'-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2^phehyl4-qύmolinyl)carbonyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :3);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(3-pyridinylacetyl)4H-l,4- benzodiazepine, trifluoroacetate (1 :3); 4-(9H-Fluoren-9-ylacetyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-oxo-4-ρhenyl-3- oxazolidinyl)acetyl]-lH-l,4-benzodiazepine, trifluoroacetate (1 :2);

4-(9-Acridinylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:3);

2,3 ,4,5-Tetrahydro-l -(1 H-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)- IH- 1 ,4- benzodiazepine, trifluoroacetate (1:2); 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[4'-(trifluoromethyl)[l,l '-biphenyl]-2- yl]carbonyl]-lH-l,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-phenoxybenzoyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2); 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-phenoxyphenyl)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[(4-methylphenyl)sulfinyl]benzoyl]-

IH- 1,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[(phenyhnethyl)amino]benzoyl]-lH-

1 ,4-benzodiazepine, trifluoroacetate (1:3); 1 ,2,3 ,5-Tetrahydro- 1 -(1 H-imidazol-4-yl-methyl)-N,N-diphenyl-4H- 1 ,4-benzodiazepine-4- carboxamide, hydrochloride; l,2,3,5-Tefrahydro-l-(lH-imidazol-4-yl-methyl)-a,7-diphenyl-4H-l,4-benzodiazepine-4- acetic acid, methyl ester, hydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepine, hydrochloride;

^■ (R)-7-Bromo-2,-3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyi)-3--

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-2,3,4,5-Tetrahyαro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-

1 H- 1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride; (R)-4-Acetyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-

1 H-l ,4-benzodiazepine, monohydrochloride;

7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(l,2,3,4-tetrahydro-l- quinolinyl)carbonyl]-lH-l,4-benzodiazepine, monohydrochloride;

N-Ethyl-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,7-diphenyl-4H-l,4- benzodiazepine-4-carboxamide, monohydrochloride;

4-[(2,3-Dihydro-lH-indol-l-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, monohydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y-lmethyl)-4-(methylsulfonyl)-3-( henylmethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, trihydrocliloride;

(R)-4-[[2-(Dime ylammo)emyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1); [2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(l-memyl-lH-imidazol-5-yl)methyl)-4-(methylsulfonyl)-

3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)- 3-(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

4-[2-(4-Chlorophenyl)-l,2-dioxoethyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, hydrochloride;

4-(l,2-Dioxopropyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, hydrochloride; - 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(4-nitrophenyl)-l,2-dioxoethyl]-7- phenyl-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(4-methoxyρhenyl)-l,2-dioxoethyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(3,3,3-trifluoro-l,2- dioxoρropyl)-lH-l,4-benzodiazepine, trifluoroacetate.(l:2);

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylacefyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(2-lH-imidazol-4^1ethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride; 8-[(Cyclohexylcarbonyl)amino]-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl-l -piperidinecarboxamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxylic acid, ethyl ester, hydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(methylsulfonyl)-3-(phenylmethyl)- lH-l,4-benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H- 1 ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-4H-l,4-benzodiazeρine, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbeιιzoyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride, 8-[(Cyclohexylcarbonyl)ammo]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N-ρhenyl-

1H- 1 ,4-benzodiazepine-4-carboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-[(2-methylphenyl)sulfonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

N-[2,3,4,5-Tefrahyα^o-l-(lH-iιnidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-i-tmdazol-4-yhne yl)-3-(ρhenylmethyl)-4H-l,4- benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride;

(3R)-7-Bromo-l-[cyano(lH-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride; (3R)-l-[2-Amino-l-(lH-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)--3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-(Dimethylammo)-l-(lH-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-Amino-l-(lH-imidazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4- (methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazeρine, dihydrochloride;

(3R)-l-[2-φime ylamino)-l-(lH-imidazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Cyano-l,3,4,5-tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-2H- 1 ,4-benzodiazepin-2-one, monohydrochloride; 7-Cyano-l,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-2H- 1 ,4-benzodiazeρin-2-one, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- phenylethyl)-lH-l,4-benzodiazepine, dihydroc-hloride;

7-Bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4- (methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-3-(cyclohexylmemyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; (S)-7-Bromo-3-(cyclohexylmethyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-methoxyphenyl)methyl]-4-

(methylsulfonyl)-lH- 1,4-benzodiazepine, dihydrochloride; 4-Acetyl-7-bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- yhnethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(3- pyridinyhnethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-8-( ydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l- naphthalenylcarbonyl)-lH-l ,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-

(phenoxymethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

N-Cyclohexyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

IH- 1 ,4-benzodiazepine-8-carboxamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-N-

(phenylmethyl)-lH-l,4-benzodiazeρine-8-carboxamide, dihydrochloride;

(R)-4-Acetyl-7-[2-[(dime ylamino)methyl]phenyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- yhnethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; (R)-4-Acetyl-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxobutyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxopropyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(2- pyridinylacetyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; (^)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methylethyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(^)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-inύdazol-4-ylmethyl)-3-(phenyhnethyl)-4-

[(trifluoromethyl)sulfonyl]-lH-l ,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazeρine, monohydrochloride;

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(phenylmethyl)-4- (phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tefrahydro-l-(lH-irmdazol-4-ylmethyl)-7-ρhenyl-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-4-[(4-fluoroρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydroc-hloride; (R)-7-Cyano-4-[(3-cyanoρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylmethyl)-4-[(l-methyl-lH-imidazol-2- yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-4-[(3-Bromophenyl)sulfonyl]-7-cyano-2,3,4,5-tefrahydro-l-(lH-in-ήdazol-4-y?l-methyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-N-[5-[[7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-(ρhenylmethyl)-lH~

1 ,4-benzodiazepin-4-yl] sulfonyl]-4-methyl-2-thiazolyl]acetamide, dihydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)-

1H-1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenyl-l,2-dioxoethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-(4-ρyridinyl)-4-[2-

(trifluoromethoxy)benzolyl] - IH- 1 ,4-benzodiazepine, trihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7- phenyl-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylacetyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

4-(2-Benzothiazolyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzazepine, trihydrochloride; (R)-7-Cyano-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-4-[(l-methylethyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(^)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4- (phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)77-Cyano-4-[(4-fluoroρhenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-4-[(3-cyanoρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyhnethyl)-lH-l,4-benzodiazepine, monohydroc-hloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylme l)-4-[(l-methyl-lH-im.idazol-2- yl)sulfόnyl]-3-(phenylmethyI)-lH-1^4-benzodiazepine, dihydrochloride;

(R)-4-[(3-Bromophenyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3- (phenylmethyl)- IH- 1,4-benzodiazepine, monohydrochloride;

(R)-N-[5-[[7-cyano-2,3,4,5-tehahydro-l-(lH-imidazol-4-ylme yl)-3-(phenylnιethyl)-lH-

1 ,4-benzodiazepin-4-yl] sulfonyl]-4-methyl-2-thiazolyl] acetamide, dihydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-yhnethyl)-3- henylmemyl)-7-(4-pyridinyl)-

1H- 1,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenyl-l,2-dioxoethyl)-7-(4- ρyridinyl)-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-

(trifluoromethoxy)benzolyl]-lH-l ,4-benzodiazepine, trihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7- phenyl-3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylacetyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine₃ monohydrochloride;

4-(2-Benzothiazolyl)-2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-7-ρhenyl- 1 H- 1 ,4- benzazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme yl)-3-(phenylmethyl)-7-(3-pyridinyl)-4-

(trifluoroacetyl)-lH-l,4-benzodiazeρine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(3- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride; 7-Bromo-3-[(l,l-dimemylemoxy)memyl]-l,2,3,4-tefrah^

5H- 1 ,4-benzodiazepin-5-one;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenoxymethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tefrahydro-3-(hydroxymethyl)-l-(lH-imidazol-4-ylmethyl)-4- (methylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(methylsulfonyl)-lH-l,4-benzodiazepine;

[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester, trihydrochloride; [4-Acetyl-7-bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH- l,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester;

N-[4-Acetyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3- (phenylmethyl)-iH-l,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester;

(R)-2,3;4,5-Tetrahy(ho-l lH-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(phenyhnethyl)- lH-l,4-benzodiazepine-7-carbonitrile, monohydrochloride;

7-Brdnlo- 1 ,2,3 ,5 -tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4H- 1 ,4- benzodiazepine-4-acetamide; 7-Bromo-4-[(dimethylamino)acetyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Bromo-4-(l,2-dioxoρroρyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-(cyclopropylcarboonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l,4-bis(lH-imidazol-4-ylme l)-3-( henyhnethyl)-lH-l,4- benzodiazepine, dihydrochloride; 7-Bromo-l,2,3,5-tetrahydro-l-(lH-in-ύdazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)-

4H-l,4-benzodiazepine-4-sulfonamide, monohydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH- l,4-benzodiazepine-7-carbonitrile, monohydrochloride; (R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-

(phenylmethyl)-4H-l,4-benzodiazepine-4-carboxamide, monohydrochloride;

N₅N-Diemyl-2,3,4,5-tefrahydro-l-(lH-irm^azol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenyhnethyl)-lH-l,4-benzodiazepine-7-carboxamide, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(l-phenyl-lH-tetrazol-5-yl)-lH- 1,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- pyrazinylcarbonyl)-4H-l ,4-benzodiazepine, monohydrochloride;

(R)-4-[7-Bromo-2,3,4,5-tetτahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepin-4-yl]-4-oxobutanoic acid, methyl ester, monohydrochloride; ( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-moφholinylcarbonyl)-3-

(ρhenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; "

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pheι-Lylmethyl)-4-[[2-(l' pyrrolidinyl)ethyl] sulfonyI]-lH-l ,4-benzodiazepine, dihydrochloride;

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(3- pyridinylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;-

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(3 yridinylmethyl)-4-(2- thienylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(ρropylsulfonyI)-3-(3- pyridinylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- pyridinylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(2- pyrimidinyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- [(trifluoromethyl)sulfonyl]-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(ρhenylmethyl)-4-

(trifluoroacetyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-

(4-pyridinyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; (R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylm^ thienylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(ρhenylsulfonyl)-7-

(4-pyridinyl)- IH- 1 ,4-benzodiazepine, dihydrochloride; ( )-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylme l)-3-(phenylmethyl)-4-(propylsulfonyl)-7-

(4-ρyridinyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(^)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4.-[(3,5- dimethyl-isoxazol-4-yl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-4-[(4-cyanophenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-^' (phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-_.(phenylmethyl)-4-[(2,2,2- trifluoroethyl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(R)-[(5-Bromo-2-tMenyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-

3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-4~{(4- methoxyphenyl)sulfonyl]'-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

N-[[7-Bromo-2,3_s4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-lH-l,4- benzodiazepin-3-yl]methyl]benzamlde, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3- (phenylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7^Cyano-l,2,3,5-tefrahydro-N,N-dimethyl-l-[(l-methyl H midazol-5-yl)methyl]-3-

(phenylmethyl)-4H-l ,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-

3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; (R)-7-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cmoro-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(phenylsulfonyl)-

3-(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(pyridin-3-ylmethyl)-4- (methylsulfonyl)- IH- 1,4-benzodiazepine, tetrahydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-lH-imidazol-4- yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trihydrochloride; (R)-7-Cωoro-2,3,4,5-tefrahydro-l-(l-memyl-in-ύdazol-5-y-hnethyl)-4-[(2-moφholm-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-moφholin-4-yl- ethyl)sulfonyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; (R)-7-Cmoro-4-[(dimethylamino)sulfonyl]-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(l-methyl-imidazol-5-yhnethyl)-4-[(4-methyl-piperidin-

4-yl-ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(l-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin- 4-yl-ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH-irmdazol-4-ylmemyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-carboxylic acid, isopropyl ester, hydrochloride; - (R)-7-Bromo-2,3,4,5-tetrahydro-4-[[2-(lH-imidazol-l-yl)ethyl]sulfonyl]-l-(lH-imidazol-.4- ylmethyl)-3-(phenylmethyl)-lH-i,4-benzodiazepine, dihydrochloride; - (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(proρylsulfonyl)-3-(3- ; pyridinylmethyl)-lH-l,4-benzodiazepine, hydrochloride; - - -

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l₅4- benzodiazepin-5-one, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-l-ylacetyl)-4-(methylsulfonyl)-3- - (phenyhnethyl)-lH-l,4-benzodiazepme, trifluoroacetate; l,2,4,5-Tetrahydro -(lH-imidazol-4-ylmethyl)-2-(2-phenylethyl)-3H-l,4-benzodiazepin-3- one;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-2-(2-phenylethyl)-lH--

1 ,4-benzodiazepine, monohydrochloride; (R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(4- pyridinylmethyl)-lH-l ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)-

1H- 1 ,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H-l,4-benzodiazepine-4-carboxamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H-l,4-benzodiazepine-4-sulfonamide, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(l-(4-cyanophenylmethyl)-imidazol-5-ylmethyl)-4-

(methylsulfonyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine-7-carbonitrile, hydrochloride; (R)-2,3,4,5-Tetrahydro-l-(l-(4-cyanopheny-lmethyl)-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-3-(phenylmemyl)-lH-l,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-4-Benzoyl-7-cyano-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylmethyl)-3-(phenylmethyl)- lH-l,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-(ρyridm-3- ylmethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(?R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-(ρyridin-3- ylmethyl)-4-(propylsulfonyl)-lH-l,4-benzodiazepine, trihydrochloride;

(^)-7-Cyano-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-yl)methyl]-3-(?^yridin-3-ylmethyl)-4- (phenylsulfonyl)- IH- 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-

(phenylmethyl)-lH-l,4-benzodiazepine; l,2,3,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-N-(l-naphthalenyl)-7-ρhenyl-4H-l,4- benzodiazepine-4-carboxamide, monohydrochloride; (S)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; -

N-[2,3,4,5-Tetrahydro-L-(lH-imidazol-4-ylmethyl)-4-(2,3-dimethylbenzoyl)-lH-l,4- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-N-[2-(dimemylammo)emyl]-2,3,4,5-tetrahydro-l-(lH-inιidazol-4-ylmethyl)-N- methyl-3-(phenylmethyl)-lfl-l ,4-benzodiazepine-4-carboxamide, trifluoroacetate (1 :2);

7-Bromd-2,3,4,5-tefrahydro-l-(lH midazol-4-ylmethyl)-4-(methylsulfonyl)-2-oxo-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-4-(2-furanylcarbonyl)-2,3,4,5-te1rahy<ho-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazeρine, trifluoroacetate (1:1); (R)-7-Cyano-2,3,4,5-tefrahy(fro-l-(lH-imidazol-4-ylmethyl)-4-[(4-nitroρhenyl)sulfonyl]-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, trifluroracetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-i[4-(4-methyl-l- ρiperazinyl)phenyl] sulfonyl]-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[(4- dimethylamino)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l ,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-[[2-(dimemylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(3- pyridinylsulfonyl)-lH-l,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme yl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH-

1,4-benzo-diazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-4-yl)methyl]-4-(methylsulfonyl)-

3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)~4-[[3-(Dimethylam o)propyl]sulfonyl]-2,3,^

7-phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride;

4-Butyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5~yl)methyl]-4-[[2-(4- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Cyano- 1 -( lH-imidazol-4-ylmethyl)-4-(4-moφholinylsul-fonyl)-3-(phenylmethyl)- 1 H- r,4-benzodiazepine, monohydrochloride; ^'-

(R)-7-Cyano-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-[(4-moφholinyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; ^"

( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-aminophenyl)sulfonyl]-3- (phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; -'

2,3,4,5-Tetrahydro-l -(lH-imidazol-4-ylmethyl)-4-[(4-pyridylthio)acetyi]-7-phenyl-lH-l, ^'4- benzodiazepine, dihydrochloride;

N-(4-Chlorophenyl)-N'-cyano-l,2,3,5-tetrahydro-l-(lH-imidazoi-4-ylmethyl)-7-pfienyl-4H-

1 ,4-benzodiazepine-4-imidamide, monohydrochloride; 4-Acetyl-7-bromo-l,2,4,5, 1 ',3'-hexahydro-l-(lH-imidazol-4-ylmethyl)spiro[3H-l,4- benzodiazepine-3,2'-[2H]indene], dihydrochloride;

7-Bromo-4- [3 -(dimethylamino)- 1 -oxopropyl] -2,3 ,4,5-tetrahydro- 1 -( 1 H-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1);

(R)-2,3,4,5-Tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-(phenylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine-7-carbonitrile, monohydrochloride;

3-(pyridin-3-yl-methyl)-lH-l,4-benzodiazepine, hydrochloride (1:1.5), trifluoroacetate

(1:0.75) salt;

4-[4-(Fluorophenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-2-(2- phenylethyl)-lH-l,4-benzodiazepine, monohydrochloride; 7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-[[2-(l- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methyl-sulfonyl)-3-(4- bromophenyhnethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahycfro-l-(lH-:i?nύ^

4-ylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-m idazol-4-ylmethyl)-4-(propyl-sulfonyl)-3-(thiazol- 4-ylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(proρylsulfonyl)-3-(4- bromophenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylmethyl)-3- yridin-3-ylmethyl)-4-

(methylsulfonyl)-l H-l ,4-benzodiazepine, trihydrochloride; (R)-7rBromo-2,3,4,5-tefrahydro-l-(lH-l-methyl-imidazol-5-ylmethyl)-3-(ρyridin-3- ylmethyl)-4-(methylsuifonyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-J-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4-. cyanophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(N-memyl-N-phenylmethyl)aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]- 3-(phenylmethyl)-lH- 1,4-benzodiazepine, monohydrochloride;

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-2,3,4,5-tetrahyα^o-l-(lH-hnidazol-4-ylmethyl)-4-(ρhenylsulfonyl)-3-(2- thienylmethyl)- 1 H- 1 ,4-benzodiazepine, hydroc-hloride; cis-2,3,4,5-Tetrahydro-l,5-bis(lH-inύdazol-4-ylmemyl)-3-(phenylmethyl)-lH-l,5- benzodiazepine-2-carboxylic acid ethyl ester, trifluoroacetate (1:2);

(R)-7-Cyano-4-[(N-piperidinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-(phenylmethyl)- lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-l-methyl-imidazol-5-ylmethyl)-3-(ρhenylmethyl)-4- (2-thienylsulfonyl)-lH- 1,4-benzodiazepine, hydrochloride;

(dimethylamino)ethyl] sulfonyl] - 1 H- 1 ,4-benzodiazepine, trihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-l-methyl-imidazol-5-ylmethyl)-3-(ρhenylmethyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; N-(Cyano)-N'-methyl-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4H-l,4- benzodiazepine-4-imidamide, hydrocliloride;

(R)-7-Cyano-4-[(2-nifroρhenyl)-sulforiyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyl-methyl)-lH-l ,4-benzodiazepine, hydrochloride; R)-7-Cyano-4-[(4-memyl-phenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-

3-(phenylmethyl)-lH-l,4-benzodiazeρine, hydrochloride;

(R)-7-Cyano-4-(butylsulfonyl)-2,3,4,5-tetrahydro-l-(lH-hnidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2- fluoro-memylρhenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-trifluoromethoxyphenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-methoxy-carbonylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol~4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyanor2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-f( ^'4= methylsulfonyl)-phenyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2₅3,4,5.-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4- trifluoromethyl)-ρhenyl)-sulfonyl)- 1 H-l ,4-benzodiazepine;

( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)--3-(phenyhnethyl)-4-((3- methoxyproρyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3,4- dimethoxyphenyl)-sulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((4-fluorophenyl)methyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(^-cyclopropylmethyl-N-ρropyl)-aminosulfonyl]-l-[(lH-imidazol-4- yl)methyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H- 1 ,4-b enzodiazepine; l,2,3,4-Tetrahydro-7-bromo-4-[(lH-imidazol-4-yl)methyl]-2-phenylmethyl-l-

(methylsulfonyl)quinoxaline;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-4-((imidazol-

4-yl)methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cymo-2,3,4,5-tefrahydro-l-(lH-iιnidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-((2- ^• thienyl)-sulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3- methylthiopropyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(((3- methylthioxo)-propyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylsulfonyl)-propyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- methylproρyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4,-30

(cyclopentylsulfonyl)- IH- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)- -((4,4,4- trifluorobutyl)-sulfonyl)-lH- 1,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-teiτahyα^o-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyL)-4-

((phenylmethyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-4-[[2-(5-(N- benzoyl)-aminomethyl)-thienyl]-sulfonyl]-lH-l,4-benzodiazepine

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-=4-[[2-(l-(3- chloro-5 -methyl-pyridin-2-yl))-pyrrolyl] -sulfonyl] - 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)- IH- 1 ,4-benzodiazepine; R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(ρhenylmethyl)-4-[((3- methyl- 1 ,2,4-oxadiazol-5-yl)-phenyl)-sulfonyl] - 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-((2,5- dimethoxyphenyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N-tetrahydroquinolinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3- (phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N,N-bis-[l -(2-methylpropyl)amino]-sulfonyl]-l-[(lH-imidazol-4- yl)methyl]-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N-methyl-N-phenyl)aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(2-(2,6-dimethylρhenyl)- ethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine; '

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(l-(N-ρhthalinndoethyl)-imidazol-5-ylmethyl)-3-

(phenylmethyl)-4-(methylsulfonyl)- IH- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-(N ,N-α^

(phenyhnethyl)-4-(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-aminoemyl)-imidazol-5-ylmethyl]-3-(phenylmethyl)-

4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(^)-4-(methanesulfonyl)-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)- lH-8-oxo-pyrimidino[4,5-e]-l,4-diazepine;

( )-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-((4-(2-methoxyethoxy)- phenyl)methyl)-4-(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-in-udazol-4-ylme l)-3-((4-(2-(dimethylamino)- ethoxy)-phenyl)methyl)-4-(phenylsulfonyl)- IH- 1 ,4-benzodiazepine; (^)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl) 4-

. (methylsulfonyl)-lH-l,4-benzodiazepine; _ - (R)-7-Cyano-2,3,4,5rtefrahydro-l-(lH-imidazol-4-ylsulfonyl)-3_^(phenylmethyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(ρhenylmethyl)-4- (phenylsulfonyl)-lH-l,-4-benzodiazepine; - •

(R)-7-Cyano^2,3,4,5-tefrahydro-l-(lH4midazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)-lH ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4-

(methylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(methylsulfonyl)-lH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(propylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-ρhenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahyα^o-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)- i -phenyl-ethyl]-4- (phenylsulfonyl)-lH-l ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l -phenyl-ethyl]-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-{S)-[(S)-l-phenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-irmdazol-4-ylmethyl)-3-(R)-[(R)-phenylcycloprδpyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahyά^o-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-ρhenylcycloρropyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4-

((2-thienyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- (methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcycloρroρyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-(R)-[(S)-phenylcyclopropyl)-4-

((2-thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-ρhenylcyclopropyl)-4-

(methylsulfonyl)- IH- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-phenylcycloρroρyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(S)-[(R)-phenylcyclopropyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-irnidazol-4-ylmethyl)-3-(S)-[(R)-phenylcyclopropyl)-4- ((2-thienyl)-sulfonyl)-lH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(S)-[(S)-ρhenylcycloρropyl)-4-

(phenylsulfonyl)- 1H-1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydrΘ-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-phenylcyclopropyl)r4~ =-

((2-thienyl)-sulfonyl)-lH-l ,4-benzodiazepine;

(^)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-iιm^azol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5- (pyridin-2-yl))-thienyl)-sulfonyl])-lH-l ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5-(l,2- isoxazol-3-yl))-thienyl)-sulfonyl])-lH-l,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρroρyl)-3-(phenylmethyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-proρyl)-3-(ρhenylmethyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

((2-thienyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((l- oxoethyl)-amino)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(methanesulfonylamino)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonylamino)- 1 H- 1 ,4-benzodiazepine.

4. The method claim I, wherein the compound has the formula

5. The method claim 1, wherein the compound has the formula

6. The method claim 1, wherein the compound has the formula

wherein

Ri is selected from Cl, Br, phenyl, pyridyl or cyano; R₂ is selected from substituted aralkyl or substituted heterocycloalkyl; R₃ is selected from substituted alkyl, substituted aryl or substituted heterocyclo; Zi is selected from CO, S0₂, C0₂, CO?NHR₅, S0₃, S0₂ _NR₅, or C(NCN)NR₅ ; R₅ is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl.

7. The method of claim-1 , wherein the compound has the formula

wherein

Ri is selected from Cl, Br, phenyl, pyridyl or cyano;

R₂ is selected from substituted aralkyl or substituted heterocycloalkyl;

Zi is selected from CO, S0₂, C0₂, CO?NHR₅, S0₃, S0₂ ?NR₅, or C(NCN)NR₅;

Prot is triphenyhnethyl or Boc; and R₅ is selected from hydrogen, lower alkyl, substituted alkyl, aryl or substituted aryl.

8. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein n is 1; r, s and t are 0 or 1; p is 0, 1 or 2;

N, W and X are selected from the group consisting of oxygen, hydrogen, R¹, R² and R³ ; -

Z and Y are selected from the group consisting of CHR⁹, S0₂, S0₃, CO, C0₂, O, NR¹⁰, S0₂

NR¹¹, CONR¹², or Z may be absent;

R⁶, R⁷, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹, R²², R²⁴, R²⁵, R²⁶, R²⁸, R²⁹,

R³⁰, R³¹, R³², R³³, R³⁴, R³⁵, R³⁶, R³⁷, and R³⁸ are selected from the group consisting of hydrogen, lower alkyl, substituted alkyl, aryl and substituted aryl; R⁴ and R are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R²³ ;

U is selected from the group consisting of sulfur, oxygen, ?NR²⁴, CO, SO, S0₂, C0₂,NR²⁵

C0₂, NR²⁶ CONR²⁷, NR²⁸ S0₂, NR²⁹ S0₂ NR³⁰, S0₂ NR³¹, NR³² CO, CONR³³, P0₂ R³⁴ and

P0₃ R³⁵ or U is absent;

R⁸ and R²³ are selected from the group consisting of hydrogen, alkyl, substituted alkyl,

■alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo and substituted heterocyclo; any two of R¹, R² and R³ may be joined to form a cycloalkyl group;

R, S and T-are selected from the group consisting of CH₂, CO and CH(CH₂)pQ wherein Q is

NR³⁶ R³⁷, OR³⁸ or CN; and

A, B, C and D are carbon; with the provisos that

V and W are not both oxygen;

W and X together may be oxygen only if Z is either absent, O, ?NR¹⁰, CHR⁹, ~N(R¹⁴)~ C(0)~, -N(R¹⁵)~S0₂ --;

R²³ may be hydrogen except when U is SO, S0₂, NR²⁵ C0₂ or ?NR²⁸ S0₂ ; and R⁸ may be hydrogen except when Z is S0₂, C0₂, ~N(R¹⁵)~S0₂,

O, NR²⁰ R²¹N NR²²

\// \// S or S .

9. The method according to claim 8, wherein the pharmaceutically acceptable salt is mesylate.

10. The method according to claim 9, wherein the compound is (R)-7-cyano-2,3,4,5- tetrahydro- 1 -( lH-imidazol-4-ylmethyl)-3 -(phenylmethyl)-4-(2-thienylsulfonyl)- IH- 1 ,4- 153 benzodiazepine, mesylate salt.

11. The method according to claim 8, wherein the compound is selected from the group consisting of: 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

8-CMoro-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-2-methyl-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-4-(l-naphthalenylcarbonyl)-l-[[l-(phenylmethyl)-lH-imidazol-5-yl]methyl]-

1 H-l ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydro-(lH-imidazol-4-yl-methyl)-4-(l -naphthalenylsulfonyl)-lH-l,4- benzodiazepine, hydrochloride; (S)-2,3,4,5-Tetτahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5"Tetrahydro-l-(lH-imidazol-4-yl-methyl)-N-methyl-N-phenyl-4H-l,4-benzodiazepine-4- carboxamide, hydrochloride;

2-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-lH-l,4-benzodiazepin-4- yl]sulfonyl]benzoic acid, methyl ester, hydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)'lH-l,4- benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenenylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, hydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-[3-(lH-imidazol-2-yl)propyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[3-Amino-3-(lH-imidazol-2-yl)propyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-lH- 1,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-methyl-4-(l-napthalenylcarbonyl)-lH-l,4- benzodiazepine, hydrochloride;

(S)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naρhthalenylmethyl)-lH- 1,4-benzodiazepine, hydrochloride; 154

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-9-methyl-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[[2-(2-Aminoethyl)-lH-imidazol-4-ylmethyl-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, trihydrochloride; l-[[2--Aminomethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-

IH- 1,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazeρin-8-yl]acetamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-mιidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-naphtho[2,3-e]- 1,4-diazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-nitro-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naphthalenylcarbonyl)-8-amino-lH-l,4- benzodiazepine, dihydrochloride; N-[2,3,4,5Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]benzamide, dihydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-i-midazol-4-ylm-ethyl)-4-(l--naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl] cyclohexanamide, dihydroc-hloride;

2,3,4,5-Tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine,'dihydrochloride;

2,3,4,5-Tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-[2-(lH-imidazol-4-yl)ethyl]-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; l-[[l-(2-Aminoethyl)-lH-imidazol-5-yl]methyl]-2,3,4,5-tetrahydro-4-naphthalenylcarbonyl)-7- phenyl- 1 H- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine-4-carboxylic acid, phenylmethyl ester;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[2-(trifluoromethoxy)benzoyl]-lH- 1,4-benzodiazepine;

1 ,2,3 ,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-N-methyl-N,7-diphenyl-4H- 1 ,4- benzodiazepine-4-carboxamide, dihydrochloride;

2,3,4,5,-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaleneylcarbonyl)-7-(l- piperidinylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride; 155

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-pyridin-2-yl-lH-

1,4-benzodiazepine, trihydrochloride;

7-(2-Furanyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcabonyl)-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-7-(2-thienyl)-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naphthalenylcarbonyl)-7-(4-pyridinyl)-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-[3-(lH-imidazol-2-yl)ρroρyl]-4-(l-naρhthalenylcarbonyl)-7-phenyl-lH- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l,4-bis(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naphthalenylmethyl)-7-phenyl-lH-l,4- benzodiazepine, trifluoroacetate; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-methoxy-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-( naphthalenylcarbonyl)-lH--l,4- -^■ .- . - .- benzodiazepine-7-carboxylic acid, dihydrochloride;

2,3,4_i5-Tefrahydro-l-(lH-imidazol-5-ylmethyl)-4-(l-naphthalenylcarbonyl)-7-cyclohexyl-lH- 1,4-benzodiazepine, 2,5 hydrochloride; _ . -

7-Butyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, dihydrochloride; . _ l-[[2-(2-Aminoethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-

7-phenyl-lH-l,4-benzodiazepine, trihydrochloride; l-[[2-(Aminomethyl)-lH-imidazol-4-yl]methyl]-2,3,4,5-tetrahydro-4-(l-naphthalenylcarbonyl)-

7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-irm^azol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8-[N,N-bis(phenyl- methyl)amino] - 1 H- 1 ,4-benzodiazepine, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8yl]phenylsulfonamide, dihydrochloride;

N-Phenyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzo-diazepine-7carboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-methylbenzamide, dihydrochloride; 156

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazeρin-8-yl]-4-methylbenzamide, dihydrochloride;

3-Crdoro-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(l-naphthalenylcarbonyl)-lH- l,4-benzo-diazepin-8-yl]benzamide, dihydrochloride; 7-Bromo-2,3,4,5,-tefrahy(ho-l-[[2-[(dimethylamino)-methyl]-lH-imidazol-4-yl]methyl]-4-(l- naphthalenylcarbonyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-(4-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

IH- 1 ,4-benzodiazepine, dihydrochloride;

7-(3-Ammophenyl)-2,3,4,5-tefrahydro-l-(lH--hnidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, trihydrochloride; l-Memyl-N-[2,3,4,5-tefrahydro-l-(lH-in-udazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH- l,4-benzodiazepin-8-yl]-lH-pyrrole-2-carboxamide, trihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-furancarboxamide, dihydroc-hloride; -7~(3-Chlorophenyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

1 H- 1 ,4-benzodiazepine, dihydrochloride;

2 Methyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthaleιιylcarbonyl)-lH-

1 ,4-benzodiazepin-8-yl]benzamide, dihydrochloride;

N-Phenyl-N'-[2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH- l,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylme yl)-4-(l-naptø

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-9-methoxy-4-(l-naphthalenylcarbonyl)-lH-l,4- diazepine, dihydrochloride; (R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-[2-(methylthio)ethyl]-4-(l- naphthalenylcarbonyl)-lH-l ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-(phenylmethyl)-

IH- 1 ,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-3-(2-hydroxyethyl)-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- IH- 1,4-benzodiazepine, trifluoroacetate;

(S)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, trifluoroacetate;

4-Acetyl-7-bromo-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -(phenylmethyl)- IH- 1 ,4- benzodiazepine, hydrochloride; 157

7-Bromo-l,2,3,5-tefrahydro-l-(lH-imidazol-4ylmethyl)-3-(phenyhnethyl)-4H-l,4- benzodiazepine-4-carboxamide, trifluoroacetate;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(me ylsulfonyl)-3-(phenylmethyl)- lH-l,4-benzodiazepine, hydrochloride; 5 4-Acetyl-2,3,4,5-tefrahy<fro-l-(lH-imidazol^ benzodiazepine, trifluoroacetate;

4-Acetyl-7-bromo-3-[(4-cUorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)- lH-l,4-benzodiazeρine, dihydroc-hloride;

4-Acetyl-2,3,4,5-tefrahycho-l-(lH--bnidazol-4-y-hnethyl)-3-(phenylmethyl)-lH-naρhtho[2,3-e]- 10 1,4-diazepine, monohydrochloride;

1H-1 ,4-benzodiazepin-8-yl]urea, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylme yl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH- , naphtho[2,3-e]- 1 ,4-diazepine, monohydrochloride; 15 - - 2,2-Dimemyl-N-[2,3,4,5-tefrahydro-l-(lH--b-nidazol-4-ylmemyl)-4-(l^'~naphthalenylcarbonyl)- - lH-l,4-benzodiazepin-8-yl]propanamide, dihydrochloride; ^••- '

■ ^{' "} 2,3,4,5-Tefrahydro -(lH-imidazol-4-ybhe yl)-4^ - benzodiazepine, monohydrochloride;

4-Acetyl-7-bromo-2,3,4,5-tefrahydro-L-(lH-imidazol-4-ylmethyl)-3-(2-Haρhthalenylmethyl)- 20 lH-l,4-benzodiazepine, dihydrochloride;-

4-Acetyl-7-bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(l-naρhthalenylmethyl)- . lH-l,4-benzodiazepine, dihydrochloride;

7-(2-Chlorophenyl)-2,3,4,5-teteahydro-l-(lH-hmdazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-

1H-1 ,4-benzodiazepine, dihydrochloride; 25 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, monohydrochloride; l-Methyl-N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH- l,4-benzodiazepin-8-yl]-2-piperidinecarboxamide, trihydrochloride;

N-[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- 30 benzodiazepin-8-yl]-4-moφholinecarboxamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-3-methylbutanamide, dihydrochloride; l,2,3,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N,7-triphenyl-4H-l,4-benzodiazepin - carboxamide, dihydrochloride; 158 l,2,3,5-Tefrahy<-ho-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-naphtho[2,3-e]-l,4- diazepine-4carboxylic acid, methyl ester, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(4-ρhenyl-l,2,3-thiadiazol-5- yl)carbonyl]- IH- 1 ,4-benzodiazepine, trifluoroacetate; 5 8-[[(Cyclohexylaιmno)carbonyl]ammo]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH- 1 ,4-benzodiazepine-4-carboxylic acid, 1 , 1 -dimethylethyl ester;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-8-[[(4-methylphenyl)sulfonyl]amino]-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine-4-carboxylic acid, 1 , 1 -dimethylethylester;

7-Bromo-l,2,3,4-tefrahy(ho-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-5H-l,4- 0 benzodiazepin-5-one, dihydrocliloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[l-oxo-3-(l-piperidinyl)propyl]-7-ρhenyl-lH-

1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(4-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 5 4-[(5-Bromo-3-pyridinyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)~7-phenyl- .

1 H-l ,4-benzodiazepine, trihydrochloride;

ylmethyl)-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-4-[4-hydroxy-3-(4-moφholinyl-methyl)benzoyl]-l-(lH-imidazol-4- 0 ylmethyl)-7-phenyl-.lH- 1,4-benzodiazepine, trihydrochloride;. ...

(S)-2,3,4,5-Tefrahydro-l-(lH-irm^azol-4-ylmethyl)-4-[(l-methyl-2-pyrrolidinyl)carbonyl]-7- phenyl-lH-l,4-benzodiazepine, trihydrochloride;.

2,3,4,5-Tefrahydro-l lH-imidazol-4-ylmethyl)-7-phenyl-4-[[2-(proρylthio)-3- pyridinyl]carbonyl]-lH-l ,4-benzodiazepine, trihydrochloride; 5 4-[(2-Chloro-6-memyl-4-pyridinyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- ρhenyl-lH-l,4-benzodiazeρine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[[2-(ρhenylthio)-3- pyridinyl]carbonyl]-lH-l ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4-methylphenoxy)-3- 30 piperidinyl]carbonyl]-7-phenyl-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxy-3-pyridinyl)carbonyl]-7-ρhenyl- lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(5-phenyl-4-oxazolyl)carbonyl]-

IH- 1,4-benzodiazepine, dihydrochloride; 159

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-3-furanyl)carbonyl]- lH-l,4-benzodiazepine, dihydrochloride; 5 2,3,4,5-Tefrahycho-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyethoxy)acetyl]-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-(4-moφholinylmethyl)benzoyl]-7

2,3,4,5-Tefrahy(ho-l-(lH-imidazol-4-y?hnemyl)-4-(4-(4-moφholinylmethyl)benzoyl]-7

2,3,4,5-Tefrahydro-l-(lH-unidazol-4-ylmethyl)-4-[4-(methylsulfonyl)benzoyl]-7-phenyl-lH- 10 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[l-oxo-3-(phenylsulfonyl)propyl]-7-phenyl-

1H-1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(3-ρyridinylacetyl)-lH- l,4benzodiazepine, trihydrochloride; -15. 2,-3,4,5-Tefrahycho-l-(lH-imidazol-4-yln ethyl)-7-phenyl-4-(2-quinoxalinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

2:3,4,5-Tefrahyα o-.l-(4H-imidazolr4 ylmethyl)-4-(4-^'isσquinolinylcarbonyl)~7-phenyl-lH-:l_^ benzodiazepine, trihydrochloride;

4-[(2-Chloro-3-pyridinyl)carbonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- 20 IH-l,4-benzodiazepine, trihydrochloride; .

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-ρyridinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; - -

4-[(2,6-Dime oxy-3-pyridinyl)carbonyl]-2,3,4,5-tefralιydro-l-(lH-imidazoi-4-ylmethyl)-7- phenyl-lH4,4-benzodiazepine, trihydrochloride; 25 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(2-pyrazinylcarbonyl)-lH-l,4- benzodiazepine, tetrahydrochloride;

4-[3-(Dimethylamino)benzoyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH- 30 1,4-benzodiazepine, trihydrochloride;

1 H- 1 ,4-benzodiazepine, dihydrochloride;

4-[(Bicyclo[4.2. 0]octa-l,3,5-trien-7-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylme yl)-7-phenyl-lH4 ,4-benzodiazepine, dihydrochloride; 160

4-(2-Cmorobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylme1hyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(2,3-Dichlorobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

N-[2-[[2,3,4,5-Tefrahydro-l-(lH-inudazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]phenyl] acetamide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydroc-hloride;

2,3,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(2-methoxybenzoyl)-7-ρhenyl-l H- 1 ,4- benzodiazepine, dihydrochloride;

4-(2,3-Dimethoxybenzoyl)-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1 ,4- benzodiazepine, dihydrochloride; 4-(2,4-Dimeth xybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-iH-l,^ benzodiazepine,- dihydrochloride; 4-(2,5-Dimethoxy?benzoyl)-2,3,4,5-te^^^ . - benzodiazepine, dihydrochloride;

4-(2,6-Dimethoxy enzoyl)-2,3,4,5-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyJ- 1H-1 ,4- benzodiazepine, dihydrochloride;

4-(2,3-Dihydroxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-([l,r-Biρhenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-

1,4-benzodiazepine, dihydrochloride; 2,3,4,5Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methylbenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(2,3-Dimethylbenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 161

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxybenzoyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(3,4-Dimemoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(3,5-Dimethoxybenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methylbenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-(l,2-Dioxo-2-ρhenylethyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[(2-Ethoxy-l-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- ρhenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naρhthalenylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 4-(Fluorophenylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4ϊ(Diphenylacefyl)^"-2,3,4,5-tefrah^ - ^{• •} . benzodiazepine, dihydrochloride;

2,3,4,5 -Tetrahydro-4-(2-hydroxy- 1 -oxo-2-phenylpropyl)- 1 -(1 H-imidazol-4-ylmethyl)_^7-phenyl- IH- 1,4-benzodiazepine, dihydrochloride; . -

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-2-ylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-3-ylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-5-ylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methyl-lH-indol-2-yl)carbonyl]-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

4-(2-Benzo---uranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3-ρyridinylcarbonyl)-lH-l,4- benzodiazepine, N-oxide, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(2-pyridinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 162

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-(2-quinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-iι dazol-4-ylmemyl)-7-ρhenyl-4-(l-isoquinolinylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride; 4-(3-Chloro-2-nifrobenzoyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-yhnethyl)-4-(2-nitrobenzoyl)-7-phenyl-lH-l,4- benzodiazepine, dihydroc-hloride;

2,3,4,5-Tetxahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-methoxy-2-nitrobenzoyl)-7-phenyl-lH- 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(lH-indol-4-ylcarbonyl)-7-phenyl-lH-l,4- benzodiazepine, dihydrochloride;

4-[(2,6Dihydroxy-3-naphthalenyl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydroc-hloride; 4-(lH-Benzimidazol-5-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-

1 H- 1 ,4-benzodiazepine, trihydrochloride;

4-(lH-Benzotriazolr5-ylcarbQnyl)-2-,3,4,5-tefrahydro-l-(lH midazol-4-ylmemyl)- -phenyl-lH-

1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-methoxy-2-quinolinyl)carbonyl]-7- phenyl-lH-1 ,4-benzodiazepine trihydrochloride;

N-[3-[[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]phenyl]-acetamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-methyl-l-oxo-2-phenylpropyl)-7-phenyl-

1H-1 ,4-benzodiazepine, dihydrochloride; 4-[2-(Dimethylamino)benzoyl]-2,3,4,5-tefrahydro-l-(lH-in-ιidazol-4-ylmethyl)-7-phenyl-lH-

1,4-benzodiazepine, trihydrochloride;

4-(3-Ethoxybenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine,dihydrochloride;

2,3,4,5-Tetrahydro-4-(2-hydroxy[l,l'-biphenyl]-3-ylcarbonyl)-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-4-[2-[(2-hydroxyethyl)thio]benzoyl]-l-(lH-imidazol-4-ylmethyl)-7-phenyl- IH- 1,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxy-l-naphthalenyl)carbonyl]-7- phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 163

2,3,4,5-Tetrahydro-4-[(2-hydroxy-4-qiunohnyl)-carbonyl]-l-(lH-imidazol-4-yhnethyl)-7- phenyl-lH-1 ,4-benzodiazepine, dihydroc-hloride;

2-[[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4-benzodiazepin-4- yl]carbonyl]benzamide, dihydroc-hloride; N-(l,l-Dimemylethyl)-2-[[2,3,4,5-tetrahydro-l-(lH-irmdazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl]carbonyl]benzamide, dihydrochloride;

N-(4-Fluorophenyl)-N'-[3-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-y]methyl)-7-phenyl-lH-l,4- benzodiazepin-4-yl]carbonyl]phenyl]urea, dihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(3-methyl-4-oxo-2-phenyl-4H-benzoρyran- 8-yl)carbonyl]-7-phenyl-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-7-phenyl-4-[3-(trifluoromethoxy)benzoyl]-lH-

1,4-benzodiazepine, dihydrochloride;

4-(2-Cyanobenzoyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzodiazepine,dihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-[[(4- memophenyl)sulfonyl] amino]benzoyl]-7-phenyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2j3,4,5-Tefrahydro-T-(lH4midazόl-4.-ylmethyl)-7-phenyl-4-(6-quinolinylcarbonyl)-l?EFl,4- benzodiazepine, trihydrochloride;

2,3 ,4,5-Tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-7-phenyl-4-(8-quinolinylcarbonyl)- 1 H- 1 ,4- benzodiazepine, trihydrochloride;

4-(Benzo[b]tluophen-2-ylcarbonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-

1H-1 ,4-benzodiazepine, dihydrochloride;

4-[[4-(Dimemylanιino)-l-naphthalenyl]-carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-7-phenyl-lH- 1,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(lH-purin-6-ylcarbonyl)-lH-l,4- benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(methoxyphenylacetyl)-7-phenyl-l H- 1 ,4- benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(5-methyl-l-phenyl-lH-pyrazol-4- yl)carbonyl] -7-phenyl- 1 H- 1 ,4-benzodiazepine,trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[2-(2-methylphenyl)-l-oxopropyl]-7-ρhenyl- 1H-1 ,4-benzodiazepine, dihydroc-hloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-[(tetrahydro-4-phenyl-2H-pyran-4- yl)carbonyl]-lH-l ,4-benzodiazepine, dihydrochloride; 164

2,3,4,5-Tefrahydro-l-(lH-iπύdazol-4-ylmemyl)-4-[2-(methylphenylaιnino)benzoyl]-7-phenyl-

1H- 1,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(4qumolinylcarbonyl)-lH-phenyl-

1H- 1 ,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-i-midazol-4-ylme yl)-7-phenyl-4-(4-quinolinylcarbonyl)-lH-l,4- benzodiazepine, N-oxide, dihydrochloride;

N-Methyl-N-(2-pyridlnylme l)-2-[[2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl- lH-l,4-benzodiazepin-4-yl]carbonyl]benzamide, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-isoquinolinylcarbonyl)-7-phenyl-lH-l,4- bezodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-naρhthalenylthio)acetyl]-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

4-[3-(3,4-Dimethoxyphenyl)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-

1,4-benzodiazepine, trifluoroacetate (1:2); 4-([l,l'-Biphenyl]-4-ylacetyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2); ^~

--. - 2,3,4v5ⁱTetrahydro-l-(-lH-imidazol-4-ylmethyl)-4 2-naρh alenylacetyl)-lH-l,4- benzodiazepine,trifluoroacetate (1 :2);

4-([l,r-Biphenyl]-2-ylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-lH-l,4- benzodiazepine,- trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-phenyl-4-quinolinyl)carbonyl]-lH-l,4- benzodiazepine, trifluoroacetate (1:3);

2,3 ,4,5-Tetrahydro-l -(lH-imidazol-4-ylmethyl)-4-(3-pyridinylacetyl)- IH- 1 ,4-benzodiazepine, ^" " trifluoroacetate (1:3); 5 4-(9H-Fluoren-9-ylacetyl)-2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-lH-l ,4- benzodiazepine, trifluoroacetate (1:2);

(S)-4-[2-(pime ylammo)-l-oxo-3-phenylproρyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4- ylmethyl)4H4 ,4-benzodiazepine, trifluoroacetate (1:3);

(S)-2,3 ,4, 5 -Tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4- [(2-oxo-4-phenyl-3 -oxazolidinyl)acetyl] -0 IH- 1,4-benzodiazepine, trifluoroacetate (1:2);

4-(9-Acridinylcarbonyl)-2,3,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)- 1H-1 ,4-benzodiazepine, trifluoroacetate (1:3);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(3-phenoxybenzoyl)-lH-l,4-benzodiazeρine, trifluoroacetate (1:2); 165

2,3,4,5-Tefrahy(ho-l-(lH-iιnidazol-4-ylme yl)-4-[[4'-(trifluoromethyl)[l,r-biphenyl]-2- yl]carbonyl]4H-l,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tefrahy⁽ho-l-(lH-iιmdazol-4-y--methyl)-4-(4-phenoxybenzoyl)-lH-l,4-benzodiazepine, trifluoroacetate (1 :2); 5 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-naphthalenylcarbonyl)-lH-l,4- benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxo-4-ρhenylbutyl)-lH-l,4- benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-ρhenoxyphenyl)acetyl]-lH-l,4-0 benzodiazepine, trifluoroacetate (1 :2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-[2-[(4-methylphenyl)sulfmyl]benzoyl]-lH-

1,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tefrahydro-l-(lH-hnidazol-4-ylmemyl)-4-[2-[(phenylmethyl)amino]benzoyl]-lH-l,4- benzodiazepine, trifluoroacetate (1 :3); -5 l,2,3,5-Tefrahydro-l-(lH-imidazol-4yl-methyl)-N,N-diphenyl-4H-l,4-benzodiazepine^"-

4carboxamide, hydrochloride; l,2,3,5-Tefrahycho-l-(lH-imidazol-4-yl methyl)-a,7-diphenyl-4PLl,4-benzodiazepine'4-acetic - acid, methyl ester, hydrochloride; . 4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l ,4- -0 benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenyhnethyl)-lH-

1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride; 5 (R)-4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-4-[[2-(dime ylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-

3-(phenylmethyl)-4H-l,4-benzodiazepine, trifluoroacetate (1:2);

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-4-[(l,2,3,4-tetrahydro-l-0 quinolinyl)carbonyl]-lH-l,4-benzodiazepine, monohydrochloride;

N-E yl-l,2,3,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-N,7-diphenyl-4H-l,4-benzodiazepine-

4-carboxamide, monohydrochloride;

4-[(2,3-Dihydro-lH-indol-l-yl)carbonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-lH-l,4-benzodiazepine, monohydrochloride; 166

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenyhnethyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, trihydrochloride;

(R)-4-[[2-(Dimethylamino)ethyl]sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7- phenyl-3-(phenyhnethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1); [2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naρhthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, cyclohexyl ester, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(l-me l-m-imidazol-5-yl)methyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

4-[2-(4-Chlorophenyl)-l,2-<hoxoethy]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-

IH- 1,4-benzodiazepine, hydrochloride;

4-(l,2-Dioxopropyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-lH-l,4- benzodiazepine, hydrochloride; 2,3,4,5-Tefrahyαro-l-(lH-imidazol-4-ylmethyl)-4-[2-(4-nitrόphenyl)-l,2-dioxoethyl]-7-phenyl-

1H-1 ,4-benzodiazepine, hydrochloride;

2,3,4,5^Tetrahydro4?-(lH-imidazor-4-ylmethyl)-4-[2-(4-methox) henyl)-i-;2-moxoem^^ phenyl-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(3,3,3-trifluoro-l,2-dioxopropyl)- IH- 1,4-benzodiazepine, trifluoroacetate (1:2);

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylacetyl)-4-(methylsulfonyl)-3- - (phenylmethyl)-lH-l,4-benzodiazeρine, monohydrochloride; • (R)-7-Bromo-2,3,4,5-tetrahydro-l-(2-lH-imidazol-4-ylethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; 8-[(Cyclohexylcarbonyl)amino]-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-lH-l,4- benzodiazepin-8-yl]-l-piperidinecarboxamide, dihydrochloride;

(R)-7-Cyano-l ,2,3,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4H-l ,4- benzodiazepine-4-carboxylic acid, ethyl ester, hydrochloride;

N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenyhnethyl)-lH-

1 ,4-benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

(R)-7-Cyano-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, dihydroc-hloride; 167

N-[2,3,4,5-Tefrahy<-ho-l-(lH-imidazol-4-ylmethyl)-4-(2-methoxy-3-methylbenzoyl)-lH-l,4- benzodiazepin8-yl]cyclohexanecarboχamide, dihydrochloride; 8-[(Cyclohexylcarbonyl)annno]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-N-phenyl-lH-

1 ,4-benzodiazepine-4-carboxamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methylphenyl)sulfonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

N-[2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(2-methoxyphenyl)carbonyl]-lH-l,4- benzodiazepin-8-yl]cyclohexanamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tefrahydro-l-(lH--h-nidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-sulfonic acid, ethyl ester, hydrochloride;

(3R)-7-Bromo-l_:[cyano(lH-imidazol-4-yl)methyl]-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride; (3R)-l-[2-Amino4-(lH-imidazol-4-yl)ethyl]-2,3,4,5-tetrahydro4-(methylsulfonyl)-3-

(phenylmethyl)4H-l,4-benzodiazepine, dihydrochloride;⁷

(3R)-H2-(Dime yl.amino)4-(lH-imidazo^

3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (3R)-l-[2-Amino-l-(lH-imidazol-4-yl)ethyl]-77bromo-2,3,4,5-tetrahydro-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(3R)-l-[2-(pimethylamino)-l-(lH-in-ύdazol-4-yl)ethyl]-7-bromo-2,3,4,5-tetrahydro-4-

(methylsulfonyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

7-Cyano- 1 ,3,4,5-tetrahydro- 1-(1 -methyl- lH-imidazol-5-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-2H-l,4-benzodiazepin-2-one, monohydrochloride; 7-Cyano-l,3,4,5-tefrahydro-l-(lH-i-midazol-4-y-lmethyl)-3-(phenylmethyl)-4-(phenylsufonyl)-

2H- 1 ,4-benzodiazepin-2-one, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2-phenylethyl)-

1 H-l ,4-benzodiazepine, dihydrochloride;

7-Bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4- (methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(methylsulfonyl)- IH- 1,4-benzodiazepine, dihydrochloride;

7-Bromo-3-[(2-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 168

(S)-7-Bromo-3-(cyclohexylme l)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride; 4-Acetyl-7-bromo-3-[(2-chloroρhenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)- lH-l,4-benzodiazepine, dihydrochloride;

4-Acetyl-7-bromo-3-[(3-chlorophenyl)methyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-

1H-1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-y?hnethyl)-3-[(4-hydroxyphenyl)methyl]-4- (methylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(3- pyridinylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tetrahydro-8-(hy(hoxymemyl)-l-(lH-iιm^azol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)- lH-l,4-benzodiazepine, dihydrochloride; 2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-naphthalenylcarbonyl)-8- --- -

(phenoxymethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

N-Cyclohexyl-2^",3,4,5-tetrahydro~l-(lH-irm^azόl-4-yIm'ethyl)-4-(l-naphmalehylcarbonyl)-4H^

1 ,4-benzodiazepine-8-carboxamide, dihydrochloride; N-(Cyclohexylmethyl)-2,3 j4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-( 1 - naphthalenylcarbonyl)-lH-l,4-benzodiazepine-8-carboxamide, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmemyl)-4-(l-naρhthalenylcarbonyl)-N-( henylmethyl)- lH-l,4-benzodiazepine-8-carboxamide, dihydrochloride; - ,

(R)-4-Acetyl-7-[2-[(dimethylamino)methyl]phenyl]-2,3,4,5-tefrahyάro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; (R)-4-Acetyl-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(jphenylmethyl)-lH-l,4- benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(l-oxobutyl)-3-(phenylmethyl)-

IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-me1hyl-l-oxopropyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-(2- pyridinylacetyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)-! H-l ,4-benzodiazepine, monohydrochloride; 169

( )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(l-methylethyl)sulfonyl]-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

[(trifluoromethyl)sulfonyl] - 1 H- 1 ,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-irnidazol-4-yhnethyl)-3-(phenylmethyl)-4-

(propylsulfonyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(? )-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(ρhenylmethyl)-4- (phenylsulfonyl)-lH- 1,4-benzodiazepine, monohydrochloride;

(propylsulfonyl)-lH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-4-[(4-fluorophenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-irnidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride; (R)-7-Cyano-4-[(3 -cyanophenyl).sulfonyl] -2,3 ,4,5-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-3 *- ~

(phenylmethyl)- IH- 1,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2^,4,5-tefrahydro.-lτ(l-H-imidazol-4-ylmethyl)-4-[(l~methyl-lH-imidazol-2~ yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-4-[(3-Bromophenyl)sulfonyl]-7cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- - (phenylmethyl)~lH-l,4-benzodiazepine, monohydrochloride;

(R)-N-[5-[[7-cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-4-yl] sulfonyl] -4-methyl-2-thiazolyl] acetamide, dihydrochloride;

4-Acetyl-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)-lH-

1,4-benzodiazepine, trihydrochloride; 2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2-phenyl-l,2-dioxoethyl)-7-(4-pyridinyl)-

IH- 1 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-7-(4-pyridinyl)-4-[2-

(trifluoromethoxy)benzoyl]-lH-l,4-benzodiazepine, trihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-7-ρhenyl-3- (phenylmethyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylacetyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

4-(2-Benzothiazolyl)-2,3,4,5-tetτahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-lH-l,4- benzazepine, trihydrochloride; 170

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-y?hne1-hyl)-3-( henylmemyl)-7-(3-pyridinyl)-4-

(1rifluoroacetyl)4H4 ,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7-(3- pyridinyl)- 1 H- 1 ,4-benzodiazepine, trihydrochloride; 7-Bromo-3-[(l,l-dimemylethoxy)methyl]-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-5H- l,4-benzodiazepin-5one;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenoxymethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

7-Bromo-2,3 ,4,5 -tetrahydro-3 -(hydroxymethyl)- 1 -(lH-imidazol-4-ylmethyl)-4- (memylsulfonyl)4H4 ,4-benzodiazepine, monohydrochloride;

7-Bromo-3-[(l,l-dimemylemoxy)memyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

[7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester, trihydrochloride; [4-Acetyl-7 romo-2,3,4,5-tefrahydro-l-(lH-irm^azol-4-ylmetiiyl)-3-(phenylmethyl)-lH-l,4- benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester; N-[4-Acetyt-2,-3,4;5-tetfahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyfinethyl)4H-i;4- ^' - - benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride;

[7-Bromo-2,3,4,5-tefrahyά^o-l-(lH-imidazol-4-ylmemyl)--4-(methyl3ulfonyl)-3-(phenylmethyl)- lH-l,4-benzodiazepin-8-yl]carbamic acid, 2-methylpropyl ester;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(ρhenylsulfonyl)-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine-7-carbonitrile, monohydrochloride;

7-Bromo-l,2,3,5-tefrahy(ho.-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4H-l,4- benzodiazepine-4-acetamide; 7-Bromo-4- [(dimethylamino)acetyl] -2,3 ,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -

(phenylmethyl)-lH-l,4-benzodiazepine;

(R)-7-Bromo-4-(l,2-dioxoproρyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-(cyclopropylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(ρropylsulfonyl)-lH-l ,4-benzodiazepine, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l,4-bis(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, dihydrochloride; 171

7-Bromo-l,2,3,5-tefrahydro4-(lH-imidazol-4-ylmemy^

1 ,4-benzodiazepine-4-sulfonamide, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine-7-carbonitrile, monohydrochloride; (R)-7-Cyano- 1 ,2,3,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmethyl)-

4H- 1 ,4-benzodiazepine-4-carboxamide monohydrochloride;

N,N-Diethyl-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l ,4-benzodiazepine-7-carboxamide, monohydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-7-phenyl-4-(l-ρhenyl-lH-tetrazol-5-yl)-lH-l,4- benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2- ρyrazinylcarbonyl)-4H- 1 ,4-benzodiazepine, monohydrochloride;

(R)-4-[7-Bromo-2,3,4,5-tefrahyα^o-l-(lH-imidazol-4-ylmethyl)-3r(phenylmethyl)-4H-l,4- benzodiazepin-4-yl]-4-oxobutanoic acid, methyl ester, monohydrochloride; (R)-7-Cyaήo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(4-moφholinocarbonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, monohydrochloride; ^*

(R)-7-Cyano?2,3,4,5-tefrahydro-l--(ffl^»im^ pyrrolidinyl)ethyl]sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(S)-2,3,4,5-T.etrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(3- pyridinylmethyl)4H4,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-7-phenyl-3-(3-pyridinylmethyl)-4-(2- thienylsulfonyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4-(ρropylsulfonyl)-3-(3- ⁱ pyridinylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride; (R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(2- pyridinylmethyl)-lH-l ,4-benzodiazepine, monohydrochloride;

2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(ρhenylmethyl)-7-(2- pyrimidinyl)-lH-l,4-benzodiazepine,dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- [(trifluoromethyl)sulfonyl] - IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-ρhenyl-3-(phenyhnethyl)-4-

(trifluoroacetyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-7-(4- pyridinyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride; 172

(R)-2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-7-(4-pyridinyl)-4-(2- tWenylsulfonyl)4H4 ,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydrol-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(phenylsufonyl)-7-(4- pyridinyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-2,3,4,5-Tefrahy<-ho-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(propylsulfbnyl)-7-(4- pyridinyl- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-(ρhenyhnethyl)-4-[(3,5- dimethyl-isoxazol-4-yl)sulfonyl]-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano4[(4-cyanoρhenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(Tl)-7-Cyanό-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2,2,2- trifluoroethyl)sulfonyl]-lH-l,4-benzodiazepine, dihydroc-hloride;

(R)-[(5-Bromo-2-tm^nyl)sulfonyl]-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,θ-,4,5-tefrahyα o-l-(lH-inn^azol-4-yImethyl)-4-[(4-memoxypheny

(phenyhnethyl)-lH-l,4-benzodiazeρine, dihydrochloride;

N-[-[7=Εromό^"-:2 3,4,5-tefrahy<fro-l-(ffi^ benzoώazepin-3-ylmethyl]benzamide, dihydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(phenylmefeyl)- 4H-l,4-benzodiazepineⁱ4-sulfonamide, hydrochloride;

(phenylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, hydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-b enzodiazepine, monohydrochloride; (R)-7-Chloro-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-(phenylsulfonyl)-3- phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-irmdazol-4-ylmethyl)-4-[(l-me l-lH-imidazol-4- yl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trihydrochloride; 173

(R)-7-Cωoro-2,3,4,5-tefrahyα^o-l-(l-memyl-iιnidazol-5-ylmethyl)-4-[(2-moφholin-4-yl- ethyl)sulfonyl]-3'-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Chloro-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-[(2-moφholin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Chloro-4-[(dimethylamino)sulfonyl]-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, monohydrochloride;

(R)-7-CUoro-2,3,4,5-tefrahy<ho-l-(l-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin-4-yl- ethyl)sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(l-methyl-imidazol-5-ylmethyl)-4-[(4-methyl-piperidin-4-yl- ethyl)sulfonyl] -3 -(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-4-[[2-(lH-imidazol-l-yl)ethyl]sulfonyl]-l-(lH-imidazol-4- ylmethyl)-3-(phenyhnethyl)-lH-l,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imida2ol-4-ylmethyl)-4-(propylsulfonyl)~3 3- ^~ pyridinylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

7-Bfom -2,3,4,5-tefrahydro-l-(l-H-imidazbl-4-ylmethyl)-3-(phenyhnethyl)4H-l,4" ° benzodiazepin-5-one,- hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-l-ylacetyl)-4-(methylsulfonyl)-3- (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate; l,2,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-2-(2-phenylethyl)-3H-l,4-benzodiazepin-3-one;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(methylsulfonyl)-2-(2-ρhenylethyl)-lH-l,4- benzodiazepine, monohydrochloride;

(T .)-2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-7-ρhenyl-3-(4- pyridinylmethyl)-lH- 1,4-benzodiazepine, dihydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(lH-imidazol-2-ylmethyl)-4-(phenylsulfonyl)-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H-l ,4-benzodiazepine-4-carboxamide, dihydrochloride; (R)-7-Cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-N,N-dimethyl-3-(3- pyridinylmethyl)-4H- 1 ,4-benzodiazepine-4-sulfonamide, dihydrochloride;

(U)-2,3,4,5-Tefrahydro-l-(l-(4cyanophenylmethyl)-imidazol-5ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine-7-carbonitrile, hydrochloride;

(R)-2,3,4,5-Tetrahydro-l-(l-(4-cyanophenylmethyl)-imidazol-4-ylmethyl)-4-(methylsulfonyl)- 3phenylmethyl)- 1 H- 1 ,4-benzodiazepine-7-carbonitrile, hydrochloride; 174

(R)-4-Benzoyl-7-Cyano-2,3,4,5-tefrahydro-l-(lH-iιm^azol-4-y-lmethyl)-3-(ρhenyhnethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-[(l-me yl-lH-imidazol-5-yl)methyl]-3-(ρyridin-3-ylmethyl)-

4-(methylsulfonyl)-lH-l,4-benzodiazepine, dihydroc-hloride; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-3-(pyridin-3-ylmethyl)-

4-(propylsulfonyl)- IH- 1 ,4-benzodiazepine, trihydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-yl)methyl]-3-(ρyridin-3-yhnethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine, dihydrochloride;

2,3,4,5-Tefrahydro-l-(lH-irm^azol-4-ylmethyl)-4-(methylsulfonyl)-7-phenyl-3-(ρhenylmethyl)- 1H4 ,4-benzodiazepine; l,2,3,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-N-(l-naphthalenyl)-7-phenyl-4H-l,4- benzodiazepine-4-carboxamide, monohydrochloride;

(S)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine, hydrochloride; N-[2,3,4,5-Tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(2,3-dimethylbeήzόyl)~lH-l-,4-- benzodiazepin-8-yl]cyclohexanecarboxamide, dihydrochloride; - - (R)-7-Cyano-N-[2-(dimethylanιino)ethyl]-2,3,4,5-tetτahydro-l-(lH-imidazδl-4-yhnethyl)~N-^' - memyl-3-(phenylmethyl)-lH-l,4-benzodiazepine-4-carboxamide, trifluoroacetate (1 :2);

7-BromΘ-2₅3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfony!)-2-oxo-3- (phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-4-(2--l-uranylcarbonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- IH- 1,4-benzodiazepine, trifluoroacetate (1:1);

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[(4-nitrophenyl)sulfonyl]-3-

(phenylmethyl)- IH- 1 ,4-benzodiazepine, trifluoroacetate; (R)-7-Cyano-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-yhnethyl)-4-[[4-(4-methyl- 1 - piperazin)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-[[(4- dimethylamino)phenyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate;

(R)-7-Bromo-4-[[2-(dimethylamino)ethyl]sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-4H-l,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(3- pyridinylsulfonyl)-lH-l,4-benzodiazepine, trihydrochloride;

2,3,4,5-Tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(methylsulfonyl)-3-(phenylmethyl)-lH^'-l,4- benzo-diazepine, dihydrochloride; 175

(R)-7-Bromo-2,3,4,5-tefrahydro-l-[(l-methyl-lH-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3-

(phenylmethyl)- 1H4 ,4-benzodiazepine, dihydrochloride;

(R)-4-[[3-(Oimemylamino)propyl]sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhn^ phenyl-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride; ( )-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,4- benzodiazepine, trihydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahyαro-l-(lH-imidazol-4-ylmethyl)-4-[[2-(4- moφhohnyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-[[2-(4- moφholinyl)ethyl] sulfonyl] -3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, dihydrochloride;

(R)-7-Cyano-l-(lH-i-midazol-4-ylmethyl)-4-(4 moφholmylsulfonyl)-a-(phenylmethyl)-lH-l,4- benzodiazepine, monohydrochloride; (R)-7-Cyano-:l-[(l-methyl-lH-imidazol-5-yl)methyl]-4-[(4-moφhoHnyl)sulfonyl-]-3-

(phenylmethyl)4H4,4-benzodiazepine, liionohydrochloride;

(R)-7-Cyano-2,3.,4,5-tetrahydro4-(-^ - -

(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

2,3,4,5-Tefrahydrρ-l-(lH-i idazol-4-ylme l)-4-[(4 pyridylthio)acetyl]-7-ρhenyl-lH-l,4- - benzodiazepine, dihydrochloride;

N-(4-Chlorophenyl)-N'-cyano-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4H-l,4- benzodiazepine-4-imidamide, monohydrochloride;

4-Acetyl-7-bromo-l,2,4,5, ,3^l-hexahydro-l-(lH-imidazol-4-ylmethyl)spiro[3H-l,4- benzodiazepine-3,2'-[2H]indene], dihydrochloride; 7-Bromo-4-[3-(dimethylamino)-l-oxopropyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-l,4-benzodiazepine, trifluoroacetate (1:1);

(phenylmethyl)-lH-l,4-benzodiazepine-7-carbonitrile, monohydrochloride;

2,3,4,5-Tetrahydro-l-[(l-methyl-lH-imidazol-5-yl)-methyl]-4-(methyl-sulfonyl)-7-phenyl-3- (pyridin-3-yl-methyl)-lH-l,4-benzodiazepine, hydrochloride (1:1.5), trifluoroacetate (1:0.75) salt;

4-[4-(Fluorophenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-2-(2-phenylethyl)-

IH- 1 ,4-benzodiazepine, monohydrochloride;

7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yl-methyl)-4-(methyl-sulfonyl)-2-(2- phenylethyl)-lH- 1,4-benzodiazepine, monohydrochloride; 176

(?R)-7-Cyano-2,3,4,5-tefrahydro-l-(l-methyl-lH-imidazol-5-ylmethyl)-4-[[2-(l- moφholinyl)ethyl]sulfonyl]-3-(phenylmethyl)-lH-l,4-benzodiazepine, dihydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-4-(methyl-sulfonyl)-3-(4- bromophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; (R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-in-ήdazol-4-ylme l)-4-(methyl-sulfonyl)-3-(thiazol-4- ylmethyl)-lH- 1,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(proρyl-sulfonyl)-3-(thiazol-4- ylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Bromo-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-4-(ρroρylsulfonyl)-3-(4- bromophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(^)-7-Bromo-2,3,4,5-tefrahydro-l-(lH-h-mdazol-4-y-bne l)-3-(pyridm-3-ylmethyl)-4-

(methylsulfonyl)-lH-l ,4-benzodiazepine, trihydrochloride;

(R)-7-Brom072,3,4,5-tefrahydro-l-(lH-l-methyl-imidazol-5-ylmethyl)-3-(pyridin-3-yhnethyl)-

4-(methylsulfonyl)-lH-l ,4-benzodiazepine, dihydrochloride; (R)-7-Cyano-2;β»,4,5-tetrahydro-l -(lH-imidazol-4-ylmethyl)-4-(phenyl-sulfonyl)-3-(4- cyanophenylmethyl)-lH-l,4-benzodiazepine, hydrochloride; ■ (R)=7~Cyano^4?ϊ(N-methyl-N-phen^

(phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano4-0ST-(tetrahydroisoqmnolme)sulfonyl]-l-[(lH-imidazøl-4-yl)methyl]-3- (phenylmethyl)-lH-l,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-4-(phenylsulfonyl)-3-(2- thienylmethyl)-lH-l,4-benzodiazeρine, hydrochloride; cis-2,3,4,5-Tetrahydro-l,5-bis(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-l,5- benzodiazepine-2-carboxylic acid ethyl ester-trifluoroacetate (1:2); (R)-7-Cyano4-[(N-ρiperidinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-(phenylmethyl)-lH-

1 ,4-benzodiazepine, monohydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahy(ho-l-(lH-l-me yl-imidazol-5-ylme yl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)-lH- 1,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρyridin-3-ylmethyl)-4-[[2- (dimethylamino)ethyl]sulfonyl]-lH-l,4-benzodiazepine, trihydrochloride;

(propylsulfonyl)-lH-l,4-benzodiazepine, hydrochloride;

N-(Cyano)-N'-methyl-l,2,3,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-7-phenyl-4H-l,4- benzodiazepine-4-imidamide, hydrochloride; 177

(R)-7-Cyano-4-[(2-nifroρhenyl)-sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyl-methyl)- IH- 1 ,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(4-memyl-ρhenyl)sulfonyl]-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenyhnethyl)-lH-l,4-benzodiazepine, hydrochloride; (R)-7-Cyano4-(butylsulfonyl)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-(ρhenylmethyl)- lH-l,4-benzodiazeρine, hydrochloride;

(R)-7-Cyano-4-[(2-trifluoro-methylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-trifluoromethylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-methoxy-carbonylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3-(phenylmethyl)-lH-l,4-benzodiazepine, hydrochloride;

(R)-7-Cyano-4-[(2-methyl-sulfonylphenyl)sulfonyl]-2,3,4,5-tetrahydro-l-(lH-imidazol-4- ylmethyl)-3 -(phenylmethyl)- IH- 1 ,4-benzodiazepine, hydrochloride; (R)-7-Cyano-2,3,4,5-tefrahydro4-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((4- methylnonyl)-phenyl)-sulforiyl)- 1 H- 1 ,4-benzodiazepine; tR)-7-Cyano-2,3A5-teftahydro-l-( ^ trifluoromethyl)-phenyl)-sulfonyl)-lH-l,4-benzodiazepine;

( )-7-Cyano-2,3,4,5-tefrahydrcr-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyi)-4-((3- -. methoxypropyl)-sulfonyl)4H4,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(ρhenylmethyl)-4-((3,4- dimethoxyρhenyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-((4-fluoroρhenyl)methyl)-4- ^'

(phenylsulfonyl)- IH- 1 ,4-benzodiazepine; (R)-7-Cyano-4-(N-cyclopropylmethyl-N-propyl)-aminosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-

3-(phenylmethyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-[(N,N-(dibutylamino))-sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)-lH-l ,4-benzodiazepine;

(R)-7-Chloro-4-(methanesulfonyl)-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3- (phenylmethyl)-lH-pyrido[3,4-e]-l,4-diazepine; l,2,3,4-Tetrahydro-7-bromo-4-[(lH-imidazol-4-yl)methyl]-2-phenylmethyl-l-

(methylsulfonyl)quinoxaline;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((imidazol-4- yl)methylsulfonyl)- 1 H- 1 ,4-benzodiazepine; 178

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-

(propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-((2-thienyl)methyl)-4-((2- thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine; 5 (R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((3- methylthiopropyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(((3- methylthioxo)-propyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-4-(((3- 10 methylsulfonyl)-propyl)-sulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2- methylpropyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-.(phenylmethyl)-4-

(cyclopentylsulfonyl)-lH-l,4-benzodiazepine; 15-^'- (R)-7-Cyano-2,3,4,5-tefrahydro-t(lH-imidazαl.4-ylmethyl)-3-(phehylnαethyl)-4-((4,4,4- trifluorobutyl)-sulfonyl)-lH-l,4-beήzodiazeρine; -^' 7 (R)-7-Cyano-2,3,4 5-tefrahydro-l-(lH Mdazol-4-ylme l)-3-v(phenylmethyl)-4- -

((phenylmethyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH--unidazol-4-ylmethyl)"3-(pheny ιethyl)-4-[[2-(5-(N- 20 berιzoyl)-aminomethyl)-thienyl]-sulfonyl]4H-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenyhnethyl)-4-[[2-(l-(3- chloro-5-methylφyridin-2-yl))-pyrrolyl]-sulfonyl]-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3^4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((4- carboxyphenyl)-sulfonyl)- IH- 1 ,4-benzodiazepine; 25 (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[((3-methyl-

1 ,2,4-oxadiazol-5-yl)-phenyl)-sulfonyl] - 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-((2,5- dimethoxyphenyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-4-[(N-tefrahydroquinolinyl)sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3- 30 (phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Cyano-4-(N,N-bis-[l-(2-methylproρyl)amino]-sulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

)phenylmethyl)- IH- 1 ,4-benzodiazepine;

( )-7-Cyano-4-[(N-methyl-N-phenyl)aιninosulfonyl]-l-[(lH-imidazol-4-yl)methyl]-3-

(phenylmethyl)4H4,4-benzodiazepine; 179

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(2-(2,6-dimethylρhenyl)-ethyl)-

4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(l-(N-phthalimidoe l)-imidazol-5-ylmethyl)-3-

(phenylmethyl)-4-methylsulfonyl)-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tefrahydro-l-[(2-(N,N-dimethylan ino)-ethyl)-imidazol-5-y]-methyy

(phenylmethyl)-4-(methylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahyά^o-l-[(2-ammoe yl)-imidazol-5-ylmethyl]-3-(phenylmethyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-7-Bromo-4-(memanesulfonyl)-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-ylmethyl)-3- (phenyhnethyl)-lH-thieno[2,3-e]-l,4-diazepine;

(R)-7-Bromo-4-(methanesulfonyl)-2,3,4,5-tetrahydro-l-[(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)-lH-thieno[3,2-e]-l,4-diazepine;

(R)-4-(memanesulfonyl)-2,3,4,5-tefrahydro-l-[(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-lH-

8 -oxo-pyrimidino [4, 5-e] - 1 ,4-diazepine; - (R)-7-Cyanor2,3,4,5-tefrahydro-l-(iH midazol-4-ylmethyl)-3-((4-(2-methόxyethoxy)-- phenyl)methyl)-4-(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

^"(R)-7-Cyano-2,3,4,^'5 efrahydro4.-(lH-i^ phenyl)methyl)-4-(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyanα,2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(ρhenyhnethyl)-4- (methylsulfonyl)- IH- 1,4-benzodiazepine; .

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-

(propylsulfonyl)-lH-l,4-benzodiazepine;

(? )-7-Cyano-2,3,4,5-tefrahydro-l-(lH-iπύdazol-4-ylsulfonyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylsulfonyl)-3-(phenylmethyl)-4-(2- thienylsulfonyl)- IH- 1 ,4-benzodiazepine;

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4- . (propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4-

(phenylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-l-ρhenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 180

7-Cyano-2,3,4,5-tefrahyά^o-l-(lH-iιnidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4- (methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahyα^o-l-(lH---midazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(propysufonyl)- 1 H- 1 ,4-benzodiazepine; 7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-ρhenyl-ethyl]-4- (methylsulfonyl)-lH-l,4-benzodiazepine;

(propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-l-ρhenyl-ethyl]-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyaho-2,3,4,5-tetrahydro-l-(lH-imidazόl-4-ylmethyl)-3-(R)-[(S)-l-phenyl-ethyl]-4-((2- thienyI)-sulfonyl)-lH-l,4-benzodiazepine; ^■'"^■ "

7-Cyano^2,3,4,5-tefrahydro4-(lH- idazol-4^

(methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-ρhenyl-ethyl]-4- (propylsulfonyl)4H-l ,4-benzodiazepine;

(phenylsulfonyl)-l H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(S)-l-phenyl-ethyl]-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4-

(methylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(R)-phenylcyclopropyl)-4- phenylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3.-(R)-[(R)-ρhenylcycloρroρyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(methylsulfonyl)-lH-l,4-benzodiazepine; 181

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- propylsulfonyl)- IH- 1 ,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-phenylcyclopropyl)-4- phenylsulfonyl)-lH-l,4-benzodiazepine; 7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(R)-[(S)-ρhenylcyclopropyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[(R)-ρhenylcycloproρyl)-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-(S)-[(R)-phenylcycloproρyl)-4- (propylsulfonyl)- IH- 1 ,4-benzodiazepine;

(phenylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-teteahydro-l-(lH-inddazol-4-ylmethyl)-3-(S) [(R.)-phenylcycloproρyl)-4-((2- thienyl)-sulfonyl)-lH- 1 ,4-benzodiazepine; 7-Cyano-2,-3_?4,5-tetrahydro-l-(lH-im^

(methylsulfonyl)-lH-l ,4-benzodiazepine;

-7-Cyano-2;3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyI)-3-(S)-[(S)-phenylcyclopropyl)-4-^* "

(propylsulfonyl)-lH-l,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(S)-[.(S)-phenylcyclopropyl)-4- (phenylsulfonyl)-lH- 1,4-benzodiazepine;

7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-(S)-[(S)-ρhenylcycloproρyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydrd-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5-

(pyridin-2-yl))-thienyl)-sulfonyl])-lH-l,4-benzodiazepine; (R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-[(2-(5-(-l,2- isoxazol-3-yl))-thienyl)-sulfonyl])-lH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρropyl)-3-(phenyhnethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahy(ho-l-(3-(lH-imidazol-2-yl)-propyl)-3-(phenylmethyl)-4- (methylsulfonyl)- IH- 1 ,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρropyl)-3-(ρhenylmethyl)-4-

(propylsulfonyl)4H4,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(3-(lH-imidazol-2-yl)-ρropyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine; 182

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(2-(lH-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(ffl-imidazol-2-yl)-ethylsulfonyl)-3-(phenylmethyl-4-

(methylsulfonyl)-lH-l,4-benzodiazepine;

(propylsulfonyl)-lH-l,4-benzodiazeρine;

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(2-(lH-imidazol-2-yl)ethylsulfonyl)-3-(phenylmethyl)-4-((2- thienyl)-sulfonyl)-lH-l,4-benzodiazepine;

(R)-7-Cymo-2,3,4,5-tefrahy(ho-l-(lH-imidazol-4-ylmemyl)-3-(iphenylmethyl)-4-((l-oxoethyl)- amino)-lH-l,4-benzodiazepine;

(R)-7-Cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-

(memanesulfonylamino)-lH-l,4-benzodiazepine; and

(R)-7-Cyano-2,3,4,5-tetrahydro-l-(lH-imidazol--4-ylmethyl)-3-(phenylmethyl)-4-

(phenylsulfonylamino)- 1 H- 1 ,4-benzodiazepine.

12. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a farnesyl transferase inhibitor compound of the formula:

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount, wherein

Ri is Cl, Br, CN, optionally substituted phenyl, or optionally substituted 2-,3- or 4-pyridyl;

R₂ is optionally substituted lower alkyl, or optionally substituted aralkyl;

R₃ and R₅ are each independently optionally substituted lower alkyl, optionally substituted aryl, or optionally substituted heterocyclo; 183

R_t is hydrogen or lower alkyl;

Zi is CO, S0₂, C0₂ or S0₂ N(R₅)-; and n is 1 or 2.

5 13. The method according to claim 12, wherein

R₂ is optionally substituted benzyl;

2-thienyl, or optionally substituted 1-piperidinyl; 10 R₄ is hydrogen, or methyl;

Zi is CO, S0₂, or S0₂ N(R₅)-;

R₅ is optionally substituted lower alkyl or optionally substituted phenyl; and n is i.

14. The method according to claim 12 wherein

R₂ is optionally substituted benzyl;

R₃ is optionally substituted lower?alkyl, optionally substituted phenyl, optionaify substituted

2-thienyl, or optionally substituted 1-piperidinyl; t is hydrogen, or methyl; . ,

20 . Z is CO, orS0₂ ; and . nis i.

15. The method according to claim 12, wherein Ri is CN;

25 R₂ is benzyl;

R₃ is n-propyl, n-butyl, 3-methoxypropyl, 2-thienyl, 5-bromo-2-thienyl, phenyl, 4- methoxyphenyl, or 1-piperidinyl; t is hydrogen;

Z is SO₂ ; and 30 n is i.

16. The method according to claim 12 wherein the compound is selected from the group consisting of: (R)-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-lH-

35 l,4-benzodiazepine-7-carbonitrile; 184

(R)-7-cyano-2,3,4,5-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-4-(l -oxobutyl)-3 -(phenylmethyl)-

1H-1 ,4-benzodiazepine;

(R)-4-[(5-bromo-2-tMenyl)sulfonyl]-7-cyano-2,3,4,5-tetrahydro4-(lH-imidazol-4-yl methyl)-3-

(phenyl methyl)- IH- 1 ,4-benzodiazepine; (R)-7-cyano-2,3,4,5-tetrahydro-l -(lH-imidazol-4-yl methyl)-4-[(4-methoxyphenyl)sulfonyl]-3-

(phenylmethyl)-lH-l,4-benzodiazeρine;

(R)-7-cyano-2,3,4,5-tefrahydro-l-(lH-iπ-ddazol-4-ylmethyl)-3-(phenyl methyl)-4-

(phenylsulfonyl)-lH-l,4-benzodiazepine;

(^)-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4- (propylsulfonyl)- 1 H- 1 ,4-benzodiazepine;

(R)-4-(butylsulfonyl)-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-

(phenylmethyl)- 1 H- 1 ,4-benzodiazepine;

(U)-7-cyano-2,3,4,5-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(l- piperidinylsulfonyl)-lH-l,4-benzodiazepine; (R)-4-(3-memoxypropylsu?Ifonyl)-7-cyano-2,3,4,5-tefrahyά^o-l-(lH-imida dl-4-ylmethyl)-3-

(phenylmethyl)- 1 H- 1 ,4-b enzodiazepine; and pharmaceutically acceptable salts .thereof.

17. The method according to claim 12 wherein the pharmaceutically acceptable salt is selected from the group consisting of the hydrochloride salt, the methanesulfonic acid salt and the trifluoroacetic acid salt.

18. The method according to claim 12 wherein the compound is (R)-2,3,4,5-tetrahydro l-(lH-i immiiddaazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-lH-l,4-benzodiazepine-7- carbonitrile.

19. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula:

1, m, r, s and t are 0 or 1; n is 0, 1 or 2;

Y is selected from the group consisting of CHR¹², S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ ?NR¹⁴, CONR¹⁵, C(NCN), C(NCN)NR¹⁶, NR¹⁷ CO, NR¹⁸ S0₂, CONR¹⁹ NR²⁰, S0₂ ? R²¹ NR²², S(0)(NR²³), S(NR²⁴)(NR²⁵), or without Y;

Z is selected from the group consisting of CR¹², S, SO, S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂

NR¹⁴, CONR¹⁵, NR²⁶ NR²⁷, ONR²⁸, NR²⁹ O, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³³ C(NCN), 186

NR³⁴ C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂, OCONR⁴⁰, S(0)(NR⁴¹), S(NR⁴ )(NR⁴³) or CHR¹² ; or without Z;

R⁷, R⁸ are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R⁴⁴; U is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂, NR⁴⁶ C0₂„ NR⁴⁷ CONR⁴⁸, NR⁴⁹ S0₂, NR⁵⁰ S0₂ NR⁵¹, S0₂ NR⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R²⁰, R²¹ , R²², R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸, R²⁹, p30 _p31 -p32 -p33 -p34 τ_j35 p36 π37 -p38 -p39 -p40 41 -p42 43 _p45 -p46 1,47 _p48 τ,49 _p50 Is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. , is. ,

R⁵¹, R⁵², R⁵³, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸ and R⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl or substituted hetercyclo;

R¹ and R are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;

R¹, R², R³, R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl,^""al?kyhyl, substituted al-kynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, ^"substituted heterocyclo, cyano, carboxy, - - carbamyl (e.g. CONH₂), substituted carbamyl (where nitrogen may be-substituted by groups - selected from hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo), alkoxycarbonyl; any two of R¹, R², R³, R⁴, R⁵ and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except - when the carbon atom bearing the substituent is part of a double bond;

R, S and T are selected from the group consisting of CH₂, CO and CH(CH₂)_P Q wherein Q is

NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; and p is 0, 1 or 2;

A, B and C are carbon, oxygen, sulfur or nitrogen; D is carbon, oxygen, sulfur or nitrogen or without D; and with the provisos:

1. When 1 and m are both 0, n is not 0;

2. R may be hydrogen except when Z is SO, or when Z is O, ?NR or S and the carbon to which it is attached is part of a double bond or when Y is S0₂, C0₂, ?NR¹⁸ S0₂,

S(0)(NR²³), or S(NR²⁴)(NR²⁵);

20. The method of claim 19, wherein the compound has the formula:

wherein r, s andt are O or 1; l is O; m is l; nis 1;

Y is selected from the group consisting of CHR¹², S0₂, S0₃, C0₂, 0, NR¹³, S0₂ ?NR¹⁴, CONR¹⁵, C(NCN), C(NCN)NR¹⁶, NR¹⁷ CO, NR¹⁸ S0₂, CONR¹⁹ NR²⁰, S0₂ NR²¹ NR²², S(0)(NR²³), S(NR²⁴)(NR²⁵), or without Y;

Z is selected from the group consisting of S, SO, S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR²⁶ NR²⁷, ONR²⁸, NR²⁹ O, N?R³⁰ S0₂ NR^31', NR³² S0₂, NR³³ C(NCN), NR³⁴ ^" C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, ? R³⁹ C0₂, OCONR⁴⁰, S(0)(NR⁴¹), or S(NR⁴²)(NR⁴³);

R⁷, R⁸ are selected from the group consisting of hydrogen, halo, nitro, cyano and U-R^4** ; ϋ is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂, ? R⁴⁶ C0₂, NR⁴⁷

CONR ,⁴4⁸8, NR ,⁴4^y9 S0₂, NR >^D5^υ0 S0₂ NR⁵¹, S0₂ NR⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; 9 -p lO _p 12 13 _p 14 _p 15 16 _p 17 _p 18 19 20 _p21 22 _p23 24 25 _p26 _p27 . , . , . , is. , is. , is. , is. , xs. , JK. , JK. , is. , is. , is. , is. , is. , is. , is. , is. , R²⁸, R²⁹,

R ,3^J0^U, τ Rι3^J1¹, τ R>32^Δ, τ R>3^J3^J, - 35

Rr.^J°, r R,3^J6^D, τ R_>3³7', r R,3^J8^δ, - Rr.3"9, r R,4^w0, τ R.4"1, τ R,4"2, r

R,4⁴6⁰, τ R,4⁴7', τ R,4^*8°, R 4⁴9^y, r R,50

R⁵¹, R⁵², R⁵³, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸ and R⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl or aryl;

R¹¹ and R⁴⁴ are selected from the group consisting of hydrogen, alkyl, substituted alkyl alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo;

R¹, R², R³ R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, 188 cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected hydrogen, alkyl, substituted alkyl, aryl or aralkyl, substituted aryl, heterocyclo, substituted heterocyclo; any two of R¹, R², R³, R⁴, R⁵ and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except when the carbon atom bearing the substituent is part of a double bond;

R, S and T are selected from the group consisting of CH₂, and CH(CH₂)_P Q wherein Q is

NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; wherein p is 0, 1 or 2; and A, B, C and D are carbon; its enantiomers, diastereomers, pharmaceutically acceptable salts and solvates thereof; with the provisos that:

1. R¹¹ may be hydrogen except when Z is SO, or when Z is O, ?NR¹³ or S and the carbon to which it is attached is part of a double bond or when Y is S0₂, C0₂, ?NR¹⁸ S0₂, ^>■ S(0)(NR²³), or S(NR²⁴)(NR²⁵); and

2. R⁴⁴ may be hydrogen except when U is SO, S0₂, NR⁴⁶ C0₂ ^"or NR⁴⁹ S0₂.

21. The method of claim 20, wherein 1, m, r, s andt are O or l;,n is 1 or 2;_.. Y is CHR¹², S0₂, S0₃, C0_2i S0₂ NR¹⁴, CONR¹⁵ or without Y;

Z is S0₂, S0₃, CO, C0₂, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, ?NR³² S0₂, NR³⁶ CO, NR³⁷ CONR³⁸, orNR³⁹ C0₂.

22. The method of claim 21 , wherein 1, r, s, and t is 0;

Y is CHR¹², S0₂, S0₂ NR¹⁴, or CONR¹⁵ or without Y; and

Z is S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ or

CONR³⁸, NR³⁹ C0₂.

23. The method of claim 22, wherein R⁷, R⁸ is halogen, nitro, cyano or U-R⁴⁴ wherein U is S, O, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, R⁴⁴ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R⁴⁶ and R⁴⁷ is hydrogen, lower alkyl, aryl substituted alkyl or aryl. 189

24. The method of claim 19, wherein the salt is of an organic or inorganic acid.

25. The method of claim 24, wherein the salt is of hydrogen chloride, hydrogen bromide, methanesulfonic acid, hydroxyethanesulfonic acid, sulfuric acid, acetic acid, trifluoroacetic acid, maleic acid, benzenesulfonic acid, toluenesulfonic acid, nitric acid, phosphoric acid, boric acid, tartaric acid, citric acid, succinic acid, benzoic acid, ascorbic acid or salicyclic acid.

26. The method of claim 19, wherein the compound is: N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-l- naphthalenesulfonamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-l- naphthalenecarboxamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N- (phenyhnethyl)methanesulforiamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tetrahydrθ-l-(lH-imidazol-4-ylmethyl)-3-quιholinyl]benzenesulfbnamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)acetamide, dihydrochloride; N-[6 romσ-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4- methoxyphenyl)methyl]methanesulfonamide, monohydrochloride;

N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(4- methylphenyl)methyl]methanesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- methylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylethyl)benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3₅4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- ethoxyphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-

(phenylmethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,3- dimethoxyphenyl)methyl]benzenesulfonamide monohydrochloride; 190

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinohnyl]-N-[(3,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(l- naphthalenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2,5- dimethylphenyl)memyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-in-ddazol-4-y-hne l)-3-quinolinyl]-N-[(3- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-qxiinolinyl]-N-[(3- chlorophenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2r fluorophenyl)methyl]benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-lefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- ---- pyridyl)memyl]benzeriesulfonamide monohydrochloride;- ⁵

N-[6-Cyano-l,2,3,4-tefra]iy o-l-[[l~(methyl)4H-imidazol-5-.yl]methyl]-3-quinolinyl]-N-

(phenylmethyl)benzenesulfonamide monohydrochloride; -

N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(memyl)-lH-imidazol-5-yl]memyl]-3-qumolinyl]-N-[(3- ^• thiophenemethyl]benzenesulfonamide monohydrochloride;

N- [6-Cyano- 1 ,2,3 ,4-tetrahydro- 1 -( 1 H-imidazol-4-ylmethyl)-3 -quinolinyl] -N-

(phenylmethyl)methanesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-

(phenylmethyl)methanesulfonamide monohydrochloride; (R)-N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-

(phenylmethyl)benzenesulfonamide monohydrochloride.

27. A method of treating a synucleinopathic subject, the method comprising, administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula:

Y is selected from the group consisting of CHR¹², S0₂, S0₃, CO, C0₂, O, NR¹³, S0₂ NR¹⁴,

S(0)(NR²³),^" and S(NR²⁴)(NR²⁵), or without Y;

Z is selected from the group consisting of S, SO, S0₂, S0₃, CO, C0₂, O, NR¹³, SO₂ ?NR¹⁴,

CONR¹⁵, NR²⁶ NR²⁷, ONR²⁸, NR²⁹ O, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³³ C(NC? ), NR³⁴

C(NCN)NR³⁵, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C02, OCONR⁴⁰, S(0)(NR⁴¹), and

S(NR⁴²)(NR⁴³);

R⁷ and R⁸ are selected from the group consisting of hydrogen, halo, nitro, cyano and U--R⁴⁴;

U is selected from the group consisting of S, O, NR⁴⁵, CO, SO, S0₂, C0₂^ NR⁴⁶ C0₂, NR⁴⁷

CONR⁴⁸, ?NR⁴⁹ S0₂, ?NR⁵⁰ S0₂ NR⁵¹, S0₂ NR⁵², NR⁵³ CO, CONR⁵⁴, P0₂ R⁵⁵ and P0₃ R⁵⁶ or without U; 9 10 _p 12 _p13 _p14 _p 15 16 17 18 _p 19 _p20 21 22 23 24 25 -p26 _p27 _p28. _p29 JK. , is. , is. , is. , is. , is. , JK. , s. , is. , is. , is. , is. , is. , is. , is. , i . , JK , is. , is. , -K. , p30 _p31 32 _p33 _p34 _p35 _p36 37 _p38 39 40 41 _p42 _p43 _p44 _p45 _p46 _p47 48 _p49 is. , is. , is , K , -K. , is. , . , is. , is. , is , is. , is. , is. , is. , is , iS , is , i , is , K. ,

R ,5^D0^υ, - Rr,5^D1¹, R ,5^o2, R⁵³, R⁵⁴, R⁵⁵, R⁵⁶, R⁵⁷, R⁵⁸, and R⁵⁹ are selected from the group consisting of hydrogen, lower alkyl, aryl, heterocyclo, substituted alkyl and aryl;

R¹¹ and R⁴⁴ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo;

R¹, R², R³, R⁴, R⁵ and R⁶ are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aralkyl, 192 cycloalkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cyano, alkoxycarbonyl, carboxy, carbamyl, and substituted carbamyl wherein substituents on the nitrogen of the substituted carbamyl are selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, aralkyl, substituted aryl, heterocyclo, and substituted

5 heterocyclo; any two of R¹, R², R³, R⁴, R⁵ and R⁶ can join to form a cycloalkyl group; any two of R¹, R², R³, R⁴, R⁵ and R⁶ together can be oxo, except when the carbon atom bearing the substituent is part of a double bond; R, S and T are selected from the group consisting of CH₂ and CH(CH₂)_P Q wherein Q is NR⁵⁷ R⁵⁸, OR⁵⁹, or CN; p is 0, 1 or 2; and

10 A, B, C arid D are carbon; its enantiomer, diastereomer, pharmaceutically acceptable salt or solvate thereof; with the provisos that:

1. Rⁿ may be hydrogen except when Z is SO, or when Z is O, ?NR¹³ or S and the carbon to which it is attached is part of a double bond or when Y is SO₂, C0₂, NR¹⁸ SO2,

15 S(0)(NR²³), or S(NR²⁴)(NR²⁵); and ,

2. R⁴⁴ may be hydrogen except whenϋ is SO, S0₂, ? R⁴⁶ C0₂ or NR⁴⁹ S0₂.

28. The method of claim 27 wherein r, s and t are 0 or 1 ;

Y is CHR¹², SO₂, SO₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵ or without Y;

,20 Z is.CR¹², S0₂, S0₃, CO, C0₂, ? R¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, R^ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z.

29. The method of claim 27 wherein r, s and t are 0 or 1 ;

Y is CHR¹², S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵ or without Y;

25 Z is CR¹², S0₂, S0₃, CO, C0₂, NR¹³, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z.

30. The method of claim 27 wherein r, s, and t is 0;

Y is CHR¹², S0₂, CO, S0₂ NR¹⁴, or CONR¹⁵ or without Y; and

30 Z is CR¹², S0₂, S0₃, CO, C0₂, S0₂ NR¹⁴, CONR¹⁵, NR³⁰ S0₂ NR³¹, NR³² S0₂, NR³⁶ CO, NR³⁷ CONR³⁸, NR³⁹ C0₂ or without Z.

31. The method of 27 wherein R⁷, R⁸ is halogen, nitro, cyano or U-R⁴⁴ wherein U is S, O, NR⁴⁶ C0₂, NR⁴⁷ CONR⁴⁸, R⁴⁴ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted 193 alkenyl, alkynyl, substituted alkynyl, aralkyl, cycloalkyl, aryl, substituted aryl, heterocyclo or substituted heterocyclo, R⁴⁶ and R⁴⁷ is hydrogen, lower alkyl, aryl substituted alkyl or aryl.

32. The method of claim 27 wherein the compound is selected from the group consisting of:

N-[6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(lH-imidazol-4-yhnethyl)-3 -quinolinyl]- 1 - naphthalenesulfonamide, dihydrochloride;

N-[6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(1 H-imidazol-4-ylmethyl)-3 -quinolinyl]- 1 - naphthalenecarboxamide, dihydrochloride; N-[6-bromo-l,2,3,4-tetrahydro-l-(lH-imidazol-4-y?hτιethyl)-3-qumolinyl]-N-

(phenylmethyl)methanesulfonamide, dihydrochloride;

N-[6-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmemyl)-3-quinolmyl]benzenesulfonaιmde, dihydrochloride;

N-[#-bromo-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-(4- methoxyphenyi methyl methanesulfonamide, monohydrochloride;

N- [6-bromo- 1 ,2,3 ,4-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -quinolinyl] -N-[(4- methylphenyl)methyl]methanesulfonamide monohydrochloride; N-[6-cyano4,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[.(3- methylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- methylphenyl)methyl]benzenesulfonamide monohydrochloride; .

N-[6-cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-yhnethyl)-3-quinolinyl]-N- (phenylethyl)benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- ethoxyphenyl)methyl]benzenesulfonamide monohydrochloride;

N- [6-Cyano- 1 ,2,3 ,4-tetrahydro- 1 -(lH-imidazol-4-ylmethyl)-3 -quinolinyl] -N-

(phenylmethyl)benzenesulfonamide monohydrochloride; N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-yhnethyl)-3-quinolinyl]-N-[(2,3- dimethoxyphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(l- naphthalenyl)methyl]benzenesulfonamide monohydrochloride; 194

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-inιidazol-4-ylme yl)-3-quinohnyl]-N-[(2,5- dimethylphenyl)methyl]benzenesulfonamide monohydrochloride; 5 N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- thiophene)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-(lH--h-nidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- chlorophenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(2- 10 fluorophenyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tetrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N-[(3- ρyridyl)methyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2,3,4-tefrahydro-l-[[l-(me l)-lH-hnidazol-5-yl]methyl]-3-quinolinyl]-N-

(phenyhnethyl)benzenesulfonamide monohydrochloride; -15 N^[6-Cyano-l,2,3,4-tefrahydro4-.[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-[(3-.- " thiophenemethyl]benzenesulfonamide monohydrochloride;

N-[6-Cyano-l,2 3,4-tefrahydro-l-(lH-imidazol-4-ylmethyl)-3-quinolinyl]-N--

(phenylmethyl)methanesulfonamide monohydrochloride;

N-[6-Cyano-l-,2,3,4-tefrahydro-ir[[l-(methyl)-lH-imidazol-5-yl]memyl]-3-quinolinyl]-^^ , 20 (phenylmethyl)methanesulfonamide monohydrochloride; .

(R)-N-[6-Cyano-l,2,3,4-tetrahydro-l-[[l-(methyl)-lH-imidazol-5-yl]methyl]-3-quinolinyl]-N-

(phenylmethyl)benzenesulfonamide monohydrochloride.

33. A method of treating a synucleinopathic subject, the method comprising, 25 administering to a synucleinopathic subject a famesyl transferase inhibitor compound of the formula:

195

or a stereoisomeric form, or a pharmaceutically acceptable acid or base addition salt form thereof, in a therapeutically effective amount.

34. The method of any of claims 1-33, wherein the synucleinopathic subject has a synucleinopathy selected from the group consisting of: Parlrinson's disease, diffuse Lewy body disease, and multiple-system atrophy disorder.

35. The method ofclaim 34 wherein the subject is a human.

36. The method ofclaim 35, wherein the effective amount comprises about lOng/kg of body weight to about lOOOmg kg of body weight at a frequency of administration from once a day to once a month.

37. The method ofclaim 36, further comprising administering to the subject an amount of one or more non-famesyl transferase inhibitor compounds effective to treat a neurological disorder.

38. The method ofclaim 37, wherein each non-famesyl transferase inhibitor compound is selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker, cathechol 0-methyl transferase inhibitor, anticholinergic, and 1NEMDA antagonist. 196

39. The method of claim 37, wherein each non-farnesyl trasferase inhibitor compound is selected from the group consisting of Memantine, Aricept, and other acetylcholinesterase inhibitors.

40. An article of manufacture comprising packaging material and a famesyl transferase inhibitor compound of any of claims 1-33, wherein the article of manufacture further comprises a label or package insert indicating that the famesyl transferase inhibitor compound can be administered to a subject for treating a synucleinopathy.

41. The article of manufacture of claim 40, wherein the synucleinopathy is selected from the group consisting of: Parkinson's disease, diffuse Lewy body disease, and multiple system atrophy disorder.

42. The article of manufacture ofclaim 40, further comprising one or more non-famesyl . transferase inhihitorcompounds effective to treat a neurological disorder. -;-. 7 :

- 43-. The article of manufacture of claim 40, wherein each-non-farnesy] transferase in-hibitor compoundis selected from the group consisting of: dopamine agonist, DOPA decarboxylase inhibitor, dopamine precursor, monoamine oxidase blocker,.cathechol.0-methyl . transferase inhibitor, anticholinergic, and -NMDA antagonist. .- -.